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Although pair bonding has been studied for several decades, only somewhat recently have researchers began studying the neural consequences of separation from a pair bond partner. Here we examined the impact of partner separation on the socially monogamous Mongolian gerbil. Using a within-subjects design, we assessed nonsocial, nonreproductive, and reproductive behavior in male gerbils pre- and post- either 4 weeks of cohabitation with or separation from a pair bond partner. We then conducted an immediate early gene study to examine the influence of partner separation on hypothalamic oxytocin and vasopressin neural responses to interactions with a novel, opposite-sex conspecific. [ABSTRACT FROM AUTHOR]

Alcohol-associated social facilitation together with attenuated sensitivity to adverse alcohol effects play a substantial role in adolescent alcohol use and misuse, with adolescent females being more susceptible to adverse consequences of binge drinking than adolescent males. Adolescent rodents also demonstrate individual and sex differences in sensitivity to ethanol-induced social facilitation and social inhibition, therefore the current study was designed to identify neuronal activation patterns associated with ethanol-induced social facilitation and ethanol-induced social inhibition in male and female adolescent cFos-LacZ rats. Experimental subjects were given social interaction tests on postnatal day (P) 34, 36, and 38 after an acute challenge with 0, 0.5 and 0.75 g/kg ethanol, respectively, and β-galactosidase (β-gal) expression was assessed in brain tissue of subjects socially facilitated and socially inhibited by 0.75 g/kg ethanol. In females, positive correlations were evident between overall social activity and neuronal activation of seven out of 13 ROIs, including the prefrontal cortex and nucleus accumbens, with negative correlations evident in males. Assessments of neuronal activation patterns revealed drastic sex differences between ethanol responding phenotypes. In socially inhibited males, strong correlations were evident among almost all ROIs (90 %), with markedly fewer correlations among ROIs (38 %) seen in socially facilitated males. In contrast, interconnectivity in females inhibited by ethanol was only 10 % compared to nearly 60 % in facilitated subjects. However, hub analyses revealed convergence of brain regions in males and females, with the nucleus accumbens being a hub region in socially inhibited subjects. Taken together, these findings demonstrate individual and sex-related differences in responsiveness to acute ethanol in adolescent rats, with sex differences more evident in socially inhibited by ethanol adolescents than their socially facilitated counterparts. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) have a wide spectrum of effects on animal behavior. A recently suggested effect involves determining the structure of individual differences, that is how the behavioral traits of an individual covary, forming the so-called behavioral syndromes. As GCs can exert their action in multiple ways, e.g., via rapid non-genomic effects or via the activation of two highly homologous members of the steroid receptor family acting as transcription factors, it is unclear how the GC modulation of behavioral syndromes takes place. We exploited a zebrafish line with a frameshift mutation in the gene encoding the GC receptor (Gr), to investigate this question. We found that lack of Gr altered the average score of several behavioral traits in the mutant line, determining reduced boldness, and increased activity and sociability. Critically, the pattern of covariation between these traits was also substantially affected by the loss of Gr. The most evident effect was an association of traits involved in boldness in the gr mutant line. This study reveals that, in zebrafish, Gr is not only involved in the modulation of the average value of behavioral traits, but also in how the behavioral traits of an individual are interrelated and determine the behavioral syndromes., Competing Interests: Conflict of interest We declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive behaviors. Despite its prevalence, effective treatments remain elusive. Recent studies have highlighted the importance of the balance between GABAergic and glutamatergic neuronal synaptic functions in ASD development. Repetitive transcranial magnetic stimulation (RTMS) is a painless and effective treatment allowed for use in depression and obsessive-compulsive disorder. However, its efficacy in treating autism is still under investigation. Low-frequency RTMS (LF-RTMS), which shows promise in reducing autism-like behaviors, is considered to regulate synaptic function., Objective: We observed and recorded the behaviors of mice to assess the impact of RTMS on their social interactions and repetitive activities. Subsequently, we examined GABAergic and glutamatergic neuronal markers along with synaptic marker proteins to understand the underlying changes associated with these behaviors., Methods: To evaluate behaviors associated with autism spectrum disorder (ASD), several behavioral tests were conducted, focusing on sociability, repetitive behaviors, locomotion, anxiety, and depression. Additionally, Western blot and immunofluorescence staining were employed to investigate the activity of GABAergic and glutamatergic neurons in the hippocampus, aiming to understand the synaptic mechanisms underlying these behaviors., Results: LF-RTMS treatment effectively relieved the social disability and normalized synaptic function in the hippocampus of ASD mice model induced by valproate (VPA). Importantly, this treatment did not lead to any adverse effects on repetitive behavior, locomotion, anxiety, or depression., Conclusion: LF-RTMS attenuated social disability without affecting repetitive behavior, locomotion, anxiety, or depression. Changes in the expression of GABAergic and glutamatergic neuronal synaptic proteins in the hippocampus were also observed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Adverse experiences due to early life stress (ELS) or parental psychopathology such as schizophrenia (SZ) have a significant implication on individual susceptibility to psychiatric disorders in the future. However, it is not fully understood how ELS affects social-associated behaviors as well as the developing prefrontal cortex (PFC)., Objective: The aim of this study was to investigate the impact of ELS and ketamine induced schizophrenia like symptoms (KSZ) on anhedonia, social behavior and anxiety-like behavior., Methods: Male and female Sprague-Dawley rat pups were allocated randomly into eight experimental groups, namely control, gestational stress (GS), GS+KSZ, maternal separation (MS), MS+KSZ pups, KSZ parents, KSZ parents and Pups and KSZ pups only. ELS was induced by subjecting the pups to GS and MS, while schizophrenia like symptoms was induced through subcutaneous administration of ketamine. Behavioral assessment included sucrose preference test (SPT) and elevated plus maze (EPM), followed by dopamine testing and analysis of astrocyte density. Statistical analysis involved ANOVA and post hoc Tukey tests, revealing significant group differences and yielding insights into behavioral and neurodevelopmental impacts., Results: GS, MS, and KSZ (dams) significantly reduced hedonic response and increased anxiety-like responses (p < 0.05). Notably, the presence of normal parental mental health demonstrated a reversal of the observed decline in Glial Fibrillary Acidic Protein-positive astrocytes (GFAP+ astrocytes) (p < 0.05) and a reduction in anxiety levels, implying its potential protective influence on depressive-like symptoms and PFC astrocyte functionality., Conclusion: The present study provides empirical evidence supporting the hypothesis that exposure to ELS and KSZ on dams have a significant impact on the on development of anxiety and depressive like symptoms in Sprague Dawley rats, while positive parenting has a reversal effect., Competing Interests: Competing interests The authors declare that they have no competing interests, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age. Experimental animals interacted with two male and two female partners in two conditions - one in which physical access was restricted (the constrained social access condition) and a second in which physical access was unrestricted (the unconstrained social access condition). Across conditions and interaction partners, there were no significant effects of lesion condition on the frequency or duration of social interactions. As a group, the hippocampus-lesioned animals generated the greatest number of communicative signals during the constrained social access condition. Amygdala-lesioned animals generated more frequent stress-related behaviors and were less exploratory. Amygdala and hippocampus-lesioned animals demonstrated greater numbers of stereotypies than control animals. Subtle, lesion-based differences in the sequencing of behaviors were observed. These findings suggest that alterations of adult social behavior are much less prominent when damage to the amygdala occurs early in life rather than in adulthood.

Humans and other animals exhibit aversive behavioral and emotional responses to unequal reward distributions compared with their conspecifics. Despite the significance of this phenomenon, experimental animal models designed to investigate social inequity aversion and delve into the underlying neurophysiological mechanisms are limited. In this study, we developed a rat model to determine the effects of socially equal or unequal reward and stress on emotional changes in male rats. During the training session, the rats were trained to escape when a sound cue was presented, and they were assigned to one of the following groups: all escaping rats [advantageous equity (AE)], freely moving rats alongside a restrained rat [advantageous inequity (AI)], all restrained rats [disadvantageous equity (DE)], and a rat restrained in the presence of freely moving companions [disadvantageous inequity (DI)]. During the test session, rats in the advantageous group (AE and AI) escaped after the cue sound (expected reward acquisition), whereas rats in the disadvantageous group (DE and DI) could not escape despite the cue being presented (expected reward deprivation). Emotional alteration induced by exposure to restraint stress under various social interaction circumstances was examined using an open field test. Notably, the DI group displayed reduced exploration of the center zone during the open field tests compared with the other groups, indicating heightened anxiety-like behaviors in response to reward inequity. Immunohistochemical analysis revealed increased c-Fos expression in the medial prefrontal and orbitofrontal cortices, coupled with reduced c-Fos expression in the striatum and nucleus accumbens under DI conditions, in contrast to the other experimental conditions. These findings provide compelling evidence that rats are particularly sensitive to reward inequity, shedding light on the neurophysiological basis for distinct cognitive processes that manifest when individuals are exposed to social equity and inequity situations., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The prairie vole (Microtus ochrogaster) is a rodent species that has been used extensively to study biological aspects of human social bonding. Nevertheless, this species has not been studied in the context of modeling social deficits characteristic of schizophrenia. Building on studies in rodents that show that sub-chronic administration of an NMDA receptor antagonist induces persistent behavioral and neurological characteristics of schizophrenia, we administered MK-801 (0.2 mg/kg, daily, for 7 days) or physiological saline to young adult (45 days old) virgin male voles. At 69 days of age, we paired these males with virgin females. 24 h later, we assessed the males' social investigation of each female across the first 5 min of a three-hour preference test, and side-by-side contact with each female during the last hour of the test. Unlike saline-treated males, MK-801-treated males did not preferentially investigate the unfamiliar female, indicating a deficit in social memory. Although males of both groups preferentially spent time with their female partner, regression analysis revealed that deficits in social memory predicted lower partner preference in MK-801-treated males. We interpret these results in the context of recent studies of the natural history of the prairie vole as well as in the context of cognitive deficits in schizophrenia and propose that the social component of episodic memory might influence an individual's capacity to form and maintain long-term social bonds., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The Roman high- (RHA) and low-avoidance (RLA) rats were bidirectionally selected and bred for, respectively, their rapid vs. extremely poor acquisition in the two-way active avoidance task. Consistent between-strain neurobehavioural differences have been found in anxiety- and stress-linked traits, as well as in schizophrenia-related phenotypes. RLAs display enhanced anxious- and stress-related phenotypes, whereas RHA rats show impulsivity, hyperactivity and attention/cognition-related impairments. Many of these typical behavioural phenotypes have been reported to be positively modulated by environmental treatments such as neonatal handling (NH). However, most studies on the Roman rat strains have been carried out in males. Thus, the present study for the first time focused on the joint evaluation of differences in novel object exploration (NOE), social interaction (SI), prepulse inhibition of the startle response (PPI), and cognitive performance and flexibility in various spatial tasks (using the Morris water maze, MWM) in females of both Roman rat strains. We also aimed at evaluating the long-lasting effects of NH treatment on the RHA vs. RLA profiles in these tests/tasks. Results show that anxiety-related behavior, as measured by the NOE test and self-grooming in the SI test, was increased in RLA rats, and dramatically reduced by NH. In the SI test RLA rats displayed diminished social interaction, which was rescued by NH. RHA females exhibited a deficit of PPI, which was not affected by NH. Spatial tasks in the MWM showed impairments of working memory, reference learning/memory and spatial reversal learning (i.e., cognitive flexibility) in RHA females. Spatial reference learning and cognitive flexibility (i.e., reversal task) showed some improvement in rats (mainly in RHAs) that had received NH during the first three weeks of life. With the exception of the SI test, the pattern of differences between female RHA vs. RLA profiles was overall consistent with what has previously been found in males of both strains, and NH treatment was able to enduringly improve some emotion-related and (spatial) cognitive outcomes in both strains. [ABSTRACT FROM AUTHOR]

It has been hypothesized that oxytocin increases the salience of social stimuli, whether the valence is positive or negative, through its interactions with the ventral tegmental area (VTA). Indeed, oxytocin neurons project to the VTA and activate dopamine neurons that are necessary for social experiences with positive valence. Surprisingly, though, there has not been an investigation of the role of oxytocin in the VTA in mediating social experiences with negative valence (e.g., social stress). Given that there are sex differences in how oxytocin regulates the salience of positively-valenced social interactions, we hypothesized that oxytocin acting in the VTA also alters the salience of social stress in a sex-dependent manner. To test this, female and male Syrian hamsters were site-specifically infused with either saline, oxytocin (9 μM), or oxytocin receptor antagonist (90 μM) into the VTA. Subjects were then exposed to either no defeat or a single, 15 min defeat by one RA. The day following social defeat, subjects underwent a 5 min social avoidance test. There was an interaction between sex and drug treatment, such that the oxytocin antagonist increased social avoidance compared to saline treatment in socially stressed females, while oxytocin decreased social avoidance compared to saline treatment in socially stressed males. Contrary to expectations, these results suggest that oxytocin signaling generally acts to decrease social avoidance, regardless of sex. These sex differences in the efficacy of oxytocin and oxytocin receptor antagonists to alter negatively-valenced social stimuli, however, should be considered when guiding pharmacotherapies for disorders involving social deficits., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Behavioural interactions between conspecifics rely on the appreciation of social cues, which is achieved through biochemical switching of pre-existing neurophysiological pathways. Serotonin is one of the major neurotransmitters in the central nervous system responsible for the modulation of physiological and behavioural traits, in particular social behaviour. The relative importance of serotonin in modulating optimal social responses to the available social information (i.e., social competence) is yet unknown. Here we investigate how serotonin and the serotonin 1 A receptor (5-HT 1A ) modulate social competence in a competitive context. In the cooperatively breeding cichlid Neolamprologus pulcher, we pharmacologically manipulated the serotonin availability and 5-HT 1A activity to test their effects on social behaviours during an asymmetric contest between the owner of a defended territory containing a shelter and an intruder devoid of a territory. In this contest, the adequate response by the intruders, the focal individuals in our study, is to show submissive behaviour in order to avoid eviction from the vicinity of the shelter. While the serotonin enhancer Fluoxetine did not affect the frequency of submission towards territory owners, reducing serotonin by a low dosage of 4-Chloro-DL-phenylalanine (PCPA) increased submissive behaviour. Furthermore, threat displays towards territory owners were reduced at high dosages of Fluoxetine and also at the lowest dosage of PCPA. 5-HT 1A activation increased threat displays by intruders, indicating that this receptor may not be involved in regulating social competence. We conclude that serotonin, but not its receptor 5-HT 1A plays an important role in the regulation of social competence., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The transition to motherhood in mammals is marked by changes in females' perception of and responsiveness to sensory stimuli from infants. Our understanding of maternally induced sensory plasticity relies most heavily on studies in uniparental, promiscuous house mice and rats, which may not be representative of rodent species with different life histories. We exposed biparental, monogamous California mouse (Peromyscus californicus) mothers and ovariectomized virgin females to one of four acoustic and olfactory stimulus combinations (Control: clean cotton and white noise; Call: clean cotton and pup vocalizations; Odor: pup-scented cotton and white noise; Call + Odor: pup-scented cotton and pup vocalizations) and quantified females' behavior and Fos expression in select brain regions. Behavior did not differ between mothers and ovariectomized virgins. Among mothers, however, those exposed to the Control condition took the longest to sniff the odor stimulus, and mothers exposed to the Odor condition were quicker to sniff the odor ball compared to those in the Call condition. Behavior did not differ among ovariectomized virgins exposed to the different conditions. Fos expression differed across conditions only in the anterior hypothalamic nucleus (AHN), which responds to aversive stimuli: among mothers, the Control condition elicited the highest AHN Fos and Call + Odor elicited the lowest. Among ovariectomized virgin females, Call elicited the lowest Fos in the AHN. Thus, reproductive status in California mice alters females' behavioral responses to stimuli from pups, especially odors, and results in the inhibition of defense circuitry in response to pup stimuli., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We examined the roles of oxytocin (OT) receptors in the prefrontal cortex (PFC) in short- and long-term social recognition and anxiety-related behaviors in mice. Mice injected with high or low doses of an OT receptor antagonist (OTA) or vehicle performed the social recognition test, the open-field test, and the light-dark transition test. In the social recognition test, with three daily trials over three consecutive days, control mice showed short-term recognition of a conspecific on all three days. In contrast, a high-dose injection of OTA impaired short-term social recognition on the second and third days, and it was impaired by a low-dose injection of OTA on the third day. These results suggested that OTA injection into the PFC dose-dependently inhibited short-term social recognition within each day. All three groups did not show any long-term social recognition across three days. OTA injection did not affect anxiety related behavior in the open-field and light-dark transition tests. Our findings demonstrated that OT receptors in the PFC played important roles in short-term social recognition., Competing Interests: Declaration of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Stress and anxiety play a role in many psychological processes including social behavior. The present study examines the effects of urocortin II (UCN II) on spontaneous parental behavior in adult prairie voles (Microtus ochrogaster). UCN II was found to increase passive parental behavior in voles while not affecting any stress-related measures. Delineating the mechanism of this change will aid in our understanding of the regulation of parenting.

Anxious depression is a prevalent disease with devastating consequences. Despite the lack of knowledge about the neurobiological basis of this subtype of depression, recently our group has identified a relationship between the LPA 1 receptor, one of the six characterized G protein-coupled receptors (LPA 1-6 ) for lysophosphatidic acid, with a mixed depressive-anxiety phenotype. Dysfunctional social behaviors, which have been related to increased activation of the hypothalamus-pituitary-adrenal (HPA) axis, are key symptoms of depression and are even more prominent in patients with comorbid anxiety and depressive disorders. Social behavior and HPA functioning were assessed in animals lacking the LPA 1 receptor. For these purposes, we first examined social behaviors in wild-type and LPA 1 receptor-null mice. In addition, a dexamethasone (DEX) suppression test was carried out. maLPA 1 -null mice exhibited social avoidance, a blunted response to DEX administration and an impaired circadian rhythm of corticosterone levels, which are features that are consistently dysregulated in many mental illnesses including anxious depression. Here, we have strengthened the previous experimental evidence for maLPA 1 -null mice to represent a good animal model of anxious depression, providing an opportunity to explore new therapeutic targets for the treatment of mood disorders, particularly this subtype of depression., Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interest. All authors have agreed with the submission in its present form, (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract The risk gene CACNA1C is strongly implicated in the etiology of all major psychiatric disorders, such as depressive disorder, bipolar disorder, autism spectrum disorder, and schizophrenia. These disorders feature high levels of comorbidity and share an overlap of symptoms; in particular, deficits in social functioning are common. Intriguingly, sex-dependent effects of CACNA1C single nucleotide polymorphisms on prevalence, health outcomes, and psychological traits have been reported, typically suggesting that women are more affected by CACNA1C mutations than men. In rodents, genetic modifications specifically targeting Cacna1c have repeatedly been linked to deficits in social behavior in male mice and rats but many studies neglect the sex-dependent effects observed in humans. Our study focused on the role of Cacna1c in regulating social behavior and communication in adult female rats. We compared social and non-social behavior together with concomitant emission of pro-social 50-kHz ultrasonic vocalizations (USV) associated with positive affect in constitutive heterozygous (Cacna1c+/−) rats to wildtype (Cacna1c+/+) littermate controls. Our results indicate that partial Cacna1c depletion leads to strongly reduced emission of 50-kHz USV and mild social deficits during female direct reciprocal social interaction. Detailed temporal analyses revealed most prominent reductions of 50-kHz USV during non-social behavior, suggesting that reduced positive affect occurs in a social context in Cacna1c+/− rats but is not specifically linked to social behavior. Finally, we observed increased self-grooming behavior in Cacna1c+/− rats, consistent with an autism-like phenotype. Our findings in rats thus support a role of Cacna1c in regulating behavioral phenotypes with relevance for several neuropsychiatric disorders. Highlights • The CACNA1C gene is involved in the etiology of neuropsychiatric disorders. • Women seem to be more affected by CACNA1C alterations than men. • In rodents, mutations of Cacna1c have been linked to reduced sociability. • In female rats, social deficits arise following partial Cacna1c depletion. • In particular, the emission of 50-kHz ultrasonic vocalizations is strongly reduced. [ABSTRACT FROM AUTHOR]

Highlights • We tested the social influence of saline-rats on the quinpirole rat model for OCD. • The quinpirole rat model has been evaluated and validated in numerous studies. • Saline-treated rat attenuated the compulsive-like behavior of a quinpirole rat. • This demonstrates that compulsive behavior is socially modulated. Abstract Here we present an empirical study that provides a basis for understanding the impact of the social environment on individuals with mental disorders. Rats treated chronically with the dopamine-agonist quinpirole offer a solid animal model for compulsive behavior that has been comprehensively evaluated and validated in numerous studies. Moreover, the method of behavioral analysis used in the quinpirole rat model has been similarly applied to the analysis of compulsive rituals in OCD patients, revealing similarities to the structure of compulsions in the quinpirole-sensitized rats. Here, we examined how compulsive checking by quinpirole-sensitized rats was modulated by the presence of a partner that was also treated with quinpirole or a partner that was treated with saline, compared to the typical expression of compulsive checking shown by rats tested alone. Our results demonstrate that the presence of a partner does indeed modulate the performance of checking behavior. Specifically, the vigor of compulsive checking was attenuated in the presence of a saline-treated partner, and augmented in the presence of a quinpirole-treated partner. This finding provides compelling evidence that social interactions modulate the expression of compulsive checking in the quinpirole rat model of OCD. This uncovering of the effectiveness of social modulation, indicates the quinpirole preparation as a paradigm for investigating the mechanisms by which the social environment modulates the development and expression of OCD. More generally, it presents a paradigm for the study of the influence of drug effects as a function of social interaction. [ABSTRACT FROM AUTHOR]

Abstract In utero and early neonatal exposure to maternal stress is linked with psychiatric disorders, and the underlying mechanisms are currently being elucidated. We used a prenatal stressor in pregnant mice to examine novel relationships between prenatal stress exposure, changes in the gut microbiome, and social behavior. Here, we show that males exposed to prenatal stress had a significant reduction in social behavior in adulthood, with increased corticosterone release following social interaction. Male offspring exposed to prenatal stress also had neuroinflammation, decreased oxytocin receptor, and decreased serotonin metabolism in their cortex in adulthood, which are linked to decreased social behavior. Finally, we found a significant difference in commensal microbes, including decreases in Bacteroides and Parabacteroides, in adult male offspring exposed to prenatal stress when compared to non-stressed controls. Our findings indicate that gestation is a critical window where maternal stress contributes to the development of aberrant social behaviors and alterations in cortical neurobiology, and that prenatal stress is sufficient to disrupt the male gut-brain axis into adulthood. [ABSTRACT FROM AUTHOR]

Abstract The term Fetal Alcohol Spectrum Disorder (FASD) describes all the deleterious consequences of prenatal alcohol exposure. Impaired social behavior is a common symptom of FASD. The zebrafish has emerged as a powerful model organism with which to examine the effects of embryonic alcohol exposure on social behavior due to an innate strong behavior, called shoaling. The relative transparency of the embryo also makes zebrafish powerful for cellular analyses, such as characterizing neural circuitry. However, as zebrafish develop, pigmentation begins to obscure the brain and other tissues. Due to mutations disrupting pigmentation, the casper zebrafish strain remains relatively transparent throughout adulthood, potentially permitting researchers to image neural circuits in vivo , via epifluorescence, confocal and light sheet microscopy. Currently, however the behavioral profile of casper zebrafish post embryonic alcohol exposure has not been completed. We report that exposure to 1% alcohol from either 6 to 24, or 24 to 26 h postfertilization reduces the social behavior of adult casper zebrafish. Our findings set the stage for the use of this important zebrafish resource in studies of FASD. [ABSTRACT FROM AUTHOR]

Abstract Autism spectrum disorder (ASD) is a pervasive, multifactorial neurodevelopmental disorder diagnosed according to deficits in three behavioral domains: communication, social interaction, and stereotyped/repetitive behaviors. Mutations in Shank genes account for ∼1% of clinical ASD cases with Shank3 being the most common gene variant. In addition to maintaining synapses and facilitating dendritic maturation, Shank genes encode master scaffolding proteins that build core complexes in the postsynaptic densities of glutamatergic synapses. Male mice with a deletion of the PDZ domain of Shank3 (Shank3B KO) were previously shown to display ASD-like behavioral phenotypes with reported self-injurious repetitive grooming and aberrant social interactions. Our goal was to extend these previous findings and use a comprehensive battery of highly detailed ASD-relevant behavioral assays including an assessment of mouse ultrasonic communication carried out on key developmental days and male and female Shank3B KO mice. We demonstrate that ASD-related behaviors, atypical reciprocal social interaction and indiscriminate repetitive grooming, are apparent in juvenile stages of development of Shank3B KO mice. Our findings underscore the importance of utilizing Shank mutant models to understand the impact of this gene in ASD etiology, whichmay enable future studies focusing on etiological gene-environment interactions in ASD. [ABSTRACT FROM AUTHOR]

Abstract Methylphenidate (MP) is a commonly prescribed psychostimulant for Attention Deficit Hyperactivity Disorder (ADHD). We recently reported behavioral and developmental effects of chronic MP use in healthy rats. The current study investigated how interrupting chronic MP treatment with weekend abstinence altered the behavioral and physiological consequences of chronic MP treatment, and if prolonged abstinence would reverse the observed effects. Male Sprague Dawley rats were assigned to one of three treatment groups: water (W); low dose (LD) MP; and high dose (HD) MP. For 13 weeks, rats had access to drink from a bottle containing 4 mg/kg MP (LD), 30 mg/kg MP (HD) or water (W) for 1 h, and 10 mg/kg MP (LD), 60 mg/kg MP (HD) or water (W) for the next 7 h, each week day. During weekends, all animals received only water as well as throughout the 5-week-long abstinence phase, which immediately followed the treatment phase. Throughout the treatment phase, regardless of weekend abstinence, chronic MP resulted in significant decreased food and fluid intake and body weight. Also, HD MP exposure resulted in the following behavioral effects: increased open field and circadian locomotor activity; increased latency to immobility and decreased time spent immobile in the forced swim test; increased center activity in the open field and percent of time spent in an open arm of the elevated-plus-maze; and increased social affiliation and memory in the Crawley's three chamber sociability test. During the prolonged (5-week) abstinence phase, all these effects were reversed while HD treated rats increased their fluid intake. These results indicated that intermittent brief abstinence periods (weekend's off-treatment) produced the same behavioral and developmental effects as those previously reported with chronic (7 days/week) MP treatment, but were reversible following a prolonged abstinence period (5 weeks). [ABSTRACT FROM AUTHOR]

Fetal Alcohol Spectrum Disorders (FASD) represent a large unmet medical need. Exposure of the developing human embryo to alcohol can lead to life-long suffering. Despite the well documented deleterious effects of alcohol on the developing fetus, pregnant women continue to drink alcohol, and FASD remains the leading cause of preventable mental retardation and other behavioral abnormalities. Particularly prevalent are the milder forms of the disease cluster, representing children who do not show obvious physical signs and who may be undiagnosed or misdiagnosed. To develop treatment and diagnostic tools, researchers have turned to animal models. The zebrafish is becoming one of the leading biomedical research organisms that may facilitate discovery of the biological mechanisms underlying this disease and the identification of biomarkers that may be used for diagnosis. Here we review the latest advances of this field, mostly focussing on the discoveries made in our own laboratory and others with zebrafish employed to analyze the effects of moderate to low level of exposure to alcohol. We argue that the zebrafish represents unique advantages, and adding information obtained with this species to the mix of other animal models will significantly increase translational relevance of animal biomedical research for the analysis of human FASD. [ABSTRACT FROM AUTHOR]

Increasing evidence shows that higher physical activity such as running and swimming exercises is associated with decreased depression-related symptoms. However, underlying mechanisms are not fully understood. This study aimed to investigate whether oxytocinergic system can mediate the antidepressant effect of swimming exercises in mice. First, male NMRI mice were subjected to swimming training for eight weeks, then animals intraperitoneally received oxytocin antagonist (L-368899) 1 h before behavioral tests. We assessed anhedonia and social behavior and behavioral despair using the sucrose preference test, social interaction test, and tail suspension test. Oxytocin levels in the brain and serum were also measured. The results showed that swimming training decreased anhedonia and behavioral despair, whereas it increased social behavior and oxytocin levels in male mice. On the other hand, a subthreshold dose of oxytocin antagonist treatment in exercised mice prevented the antidepressant effect of swimming exercise via increased anhedonia and behavioral despair and decreased social behavior compared to the swimming training group. However, the blockade of oxytocin receptors did not affect oxytocin levels in exercised mice. Overall, these findings suggest that oxytocinergic system can play a role in mediating the antidepressant-like effect of swimming training in mice. • Swimming training reduces depression-related symptoms in animal models. • Swimming training increases brain and serum oxytocin levels in mice. • Oxytocin blockade prevents antidepressant-like effects of swimming training in mice [ABSTRACT FROM AUTHOR]

The medial amygdala (MeA) controls several types of social behavior via its projections to other limbic regions. Cells in the posterior dorsal and posterior ventral medial amygdala (MePD and MePV, respectively) project to the bed nucleus of the stria terminalis (BNST) and these pathways respond to chemosensory cues and regulate aggressive and defensive behavior. Because the BNST is also essential for the display of stress-induced anxiety, a MePD/MePV-BNST pathway may modulate both aggression and responses to stress. In this study we tested the hypothesis that dominant animals would show greater neural activity than subordinates in BNST-projecting MePD and MePV cells after winning a dominance encounter as well as after losing a social defeat encounter. We created dominance relationships in male and female Syrian hamsters (Mesocricetus auratus), used cholera toxin b (CTB) as a retrograde tracer to label BNST-projecting cells, and collected brains for c-Fos staining in the MePD and MePV. We found that c-Fos immunoreactivity in the MePD and MePV was positively associated with aggression in males, but not in females. Also, dominant males showed a greater proportion of c-Fos+ /CTB+ double-labeled cells compared to their same-sex subordinate counterparts. Another set of animals received social defeat stress after acquiring a dominant or subordinate social status and we stained for stress-induced c-Fos expression in the MePD and MePV. We found that dominant males showed a greater proportion of c-Fos+ /CTB+ double-labeled cells in the MePD after social defeat stress compared to subordinates. Also, dominants showed a longer latency to submit during social defeat than subordinates. Further, in males, latency to submit was positively associated with the proportion of c-Fos+ /CTB+ double-labeled cells in the MePD and MePV. These findings indicate that social dominance increases neural activity in BNST-projecting MePD and MePV cells and activity in this pathway is also associated with proactive responses during social defeat stress. In sum, activity in a MePD/MePV-BNST pathway contributes to status-dependent differences in stress coping responses and may underlie experience-dependent changes in stress resilience., Competing Interests: Declaration of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

As social beings, animals and humans alike make real life decisions that are often influenced by other members. Most current research has focused on the influence of same-sex peers on individual decision-making, with potential opposite sex effect scarcely explored. Here, we developed a behavioral model to observe food foraging decision-making in female rats under various social situations. We found that female rats preferred to forage food from male over female rats or from the no-rat storage side. Female rats were more likely to forage food from familiar males than from unfamiliar. This opposite-sex preference was not altered by the lure of sweet food, or with estrous cycle, nor under stress conditions. These results suggest that the opposite sex influences food foraging decision-making in female rats. The behavioral model established could facilitate future investigation into the underlying neurobiological mechanisms., Competing Interests: Competing interests The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Prenatal and early postnatal infection have been associated with changes in microglial activity and the development of psychiatric disorders. Here, we investigated the effect of prenatal immune activation and postnatal immune challenge, alone and combined, on behavior and microglial cell density in female Wistar rats. Pregnant rats were injected with poly I:C to induce a maternal immune activation (MIA). Their female offspring were subsequently exposed to a lipopolysaccharide (LPS) immune challenge during adolescence. Anhedonia, social behavior, anxiety, locomotion, and working memory were measured with the sucrose preference, social interaction, open field, elevated-plus maze, and Y-maze test, respectively. Microglia cell density was quantified by counting the number of Iba-1 positive cells in the brain cortex. Female MIA offspring were more susceptible to the LPS immune challenge during adolescence than control offspring as demonstrated by a more pronounced reduction in sucrose preference and body weight on the days following the LPS immune challenge. Furthermore, only the rats exposed to both MIA and LPS showed long-lasting changes in social behavior and locomotion. Conversely, the combination MIA and LPS prevented the anxiety induced by MIA alone during adulthood. MIA, LPS, or their combination did not change microglial cell density in the parietal and frontal cortex of adult rats. The results of our study suggest that the maternal immune activation during pregnancy aggravates the response to an immune challenge during adolescence in female rats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Monogamous, pair-bonded animals coordinate intra-pair behavior for spatially separated challenges including territorial defense and nest attendance. Paired California mice, a monogamous, territorial and biparental species, approach intruders together or separately, but often express behavioral convergence across intruder challenges. To gain a more systems-wide perspective of potential mechanisms contributing to behavioral convergence across two conspecific intruder challenges, we conducted an exploratory study correlating behavior and receptor mRNA (Days 10 and 17 post-pairing). We examined associations between convergence variability in pair time for intruder-oriented behaviors with a pair mRNA index for oxytocin (OXTR), androgen (AR), and estrogen alpha (ERα) receptors within the medial amygdala (MeA) and the anterior olfactory nucleus (AON), brain regions associated with social behavior. An intruder behavior index revealed a bimodal distribution of intruder-related behaviors in Challenge 1 and a unimodal distribution in Challenge 2, suggesting population behavioral convergence, but no significant correlations with neuroendocrine measures. However, OXTR, AR, and ERα mRNA in the MeA were positively associated with convergence in individual intruder-related behaviors, suggesting multiple mechanisms may influence convergence. Mice could also occupy the nest during intruder challenges and convergence in nest attendance was positively correlated with MeA OXTR. At an individual level, nest attendance was positively associated with MeA ERα. Vocalizations were positively associated with AR and ERα mRNA. No positive associations were found in the AON. Overall, neuroendocrine receptors were implicated in convergence of a monogamous pair's defense behavior, highlighting the potential importance of the MeA as part of a circuit underlying convergence., Competing Interests: Declaration of Competing Interest none., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Autism spectrum disorders (ASD) are diagnosed based on the behavioral criteria of impaired social interaction, defective communication and repetitive behaviors. Psychiatric comorbidities, such as anxiety and intellectual disability, are commonly present in ASD. The BTBR T+ Itpr3tf/J (BTBR) mice display a range of autistic phenotypes, yet whether this mouse model is appropriate to study psychiatric comorbidity in ASD remains unclear. We addressed this issue by subjecting the BTBR animals to three-chambered apparatus, open field, object attention test and elevated open platform. Compared to C57BL/6J control mice, the BTBR mice displayed hyperactivity in most of the tests. In the three-chamber assessment, they exhibited deficits in sociability. In the open field, more grooming and thigmotaxis and less rearing behaviors were observed. They also showed impaired object-based attention. On the elevated open platform, the BTBR animals stayed more to the edges than in the center of the platform. To further examine the properties of this test, naïve C57BL/6J mice were randomly administrated with saline or an anxiogenic substance, caffeine. The caffeine group demonstrated a similar behavioral pattern as the BTBR mice. When the saline group was re-exposed to the same platform, the time they stayed in the center substantially increased, likely due to reduced anxiety by habituation. These results indicate that the BTBR were more anxious than control mice on the open platform. Taken together, the BTBR strain exhibit emotional and cognitive impairments in addition to autistic behaviors, suggesting that they can be a valid model for ASD with psychiatric comorbidity. [ABSTRACT FROM AUTHOR]

Olfactory signals, including the scent of urine, are thought to be processed by specific brain regions, such as the medial amygdala (Me), and regulate sexual behavior in a sex-dependent manner. We aimed to reveal the sex-specific neural circuit from the accessory olfactory bulb (AOB) to Me by using a transgenic mouse. We quantified the long-lasting green fluorescent protein (GFP) expression profile, which was controlled by the c-fos promotor in a sex-dependent manner by the scent of urine. Female urine predominantly activated neurons of the posterodorsal medial amygdala (MePD) in male mice and the posteroventral medial amygdala (MePV) in female mice. Male urine, in contrast, generated the opposite pattern of activation in the Me. Secondary, the selective artificial activation of these circuits was used to examine their specific behavioral function, by using a dual Cre-loxP viral infection. AAV-hSyn-FLEX-hM3Dq-EGFP–the designer receptor exclusively activated by a designer drug–was infused into the AOB after infection with trans-synaptic AAV(DJ)-CMV-mCherry-2A-Cre-TTC into either the MePD or the MePV. Double virus-transfected mice were injected with hM 3 Dq activator and their sexual behavior was monitored. However, selective activation of sex-dependent circuits, i.e., the AOB-MePD or AOB-MePV, did not significantly alter mounting or attack behavior in male mice. There were clear sex differences in the pheromone conveying circuits in the AOB-Me of mice. The sex-dependent functional activation of the Me, however, no effect on behavior. This suggests that a diverse number of nuclei and brain areas are likely to function in concert to successfully facilitate sexual and aggressive behaviors. [ABSTRACT FROM AUTHOR]

Calsyntenin-2 (Clstn2) is the synaptic protein that belongs to the super family of cadherins, playing an important role in learning and memory. We recently reported that Clstn2 knockout mice (Clstn2-KO) have a deficit of GABAergic interneurons coupled with hyperactivity and deficient spatial memory. Given, that impaired functioning of GABA receptors is linked to several psychopathologies, including anxiety and autism, we sought to further characterize Clstn2-KO mice with respect to emotional and social behavior. Clstn2-KO males and females were tested in the elevated plus-maze (EPM), open field (OF), forced swim test, social affiliation and recognition test, social transmission of food preference (STFP), dyadic social interactions and marble burying test. Clstn2-KO mice demonstrated high exploration and hyperactivity in the dimly lit EPM that affect anxiety parameters. In contrast, in a more adverse situation in the OF have increased emotionality in Clstn2-KO males, not females. Assessment of hyperactivity for prolong period in the OF showed that Clstn2-KO animals were able to decline their hyperactivity, but their ambulation still remained higher than in WT littermates. Additionally, Clstn2-KO mice expressed stereotyped behavior. Strikingly, analysis of social behavior identified deficient social motivation and social recognition only in Clstn2-KO males, but not in females. Further analysis of social communication in the STFP and direct observation of agonistic interactions confirmed the reduced social behavior in Clstn2-KO males. Altogether, current results showed Clstn2 gene and sex interactions on socio-emotional performance in mice, suggesting a possible role of calsyntenin2 in psychopathological mechanisms of autism. [ABSTRACT FROM AUTHOR]

MicroRNA124a (miR124a) has emerged recently as a key player for multiple neuropsychiatric disorders including depression, anxiety, alcoholism, and cocaine addiction. Although we have previously reported that miR124a and its target the brain-derived neutrophic factor (BDNF) play an important role in autism-like behaviors, the molecular and behavioral dysfunctions remain unknown. The aim of this study was to understand the effects of sustained decreases in miR124a and increases of BDNF in the dentate gyrus (DG) on neonatal isolation-induced anxiety-and autism like behaviors in rats. Here we report that lentiviral-mediated silencing of miR124a in the adult DG attenuated neonatal isolation-induced anxiety-like behavior in the elevated plus maze (EPM) and open-field (OF) tests. Also, miR124a silencing decreased autism-like phenotype in the marble burying test (MBT), self-grooming (SG), and social interaction tests. Pearson’s correlations demonstrated that high levels of BDNF, a direct target of miR124a, were negatively correlated with miR124a expression. Interestingly, viral-mediated BDNF overexpression in the DG also reversed the neonatal isolation-induced anxiety-and autism like phenotypes. Collectively, these findings suggest that miR124a, through its target BDNF, may influence neonatal isolation-induced anxiety-and autism like behaviors. In conclusion, these results do support the hypothesis that miR124a in discrete hippocampal areas contributes to anxiety- and autism-like behaviors and may be involved in the neuroadaptations underlying the development of autism spectrum disorders as a persistent and lasting condition, and therefore provide a clearer mechanistic framework for understanding the physiopathology of such psychiatric illnesses. [ABSTRACT FROM AUTHOR]

Social behavior is evolutionary conserved, and is thought to be evolved since it increased reproductive and survival fitness of living species. In humans, disturbances of social behavior are a peculiar pathological trait of neurodevelopmental disorders, namely autism spectrum disorder (ASD). ASD is defined by deficits in two core domains (social interaction/communication and repetitive/restrictive behaviors), which emerge during early postnatal development. ASD has a strong genetic component: copy number variations, de novo and familial mutations, as well as epigenetic modifications have been reported in a huge number of genes. Recent studies in mice demonstrate that mutations in a wide variety of ASD-associated genes can cause neurodevelopmental defects, which subsequently result in social behavior disturbances during early postnatal age and adulthood. From these studies, it clearly emerges that functionally interrelated cellular mechanisms underlie social behavior and its disturbances in ASD. Indeed, most of ASD-associated genes control neuronal differentiation and migration, growth of neuronal connections and synaptic function. Here we will present the recent advances in understanding the genetic determinants of social behavior, as they emerge from the study of ASD mouse models, and discuss the importance of these studies for the development of novel therapeutic approaches to overcome social disturbances in ASD. [ABSTRACT FROM AUTHOR]

Phencyclidine (PCP) has been suggested to induce symptoms of schizophrenia. However, animal models using PCP administration have produced ambiguous results thus far. It seems that acute effects are similar to symptoms of schizophrenia, however, it is not clear if PCP can induce permanent behavioral changes that reflect schizophrenic-like symptoms. Therefore, we assessed the ability of chronic PCP administration (3 mg/kg, 14 days) to induce short or long lasting behavioral changes in rats. Social behavior, including ultrasonic vocalizations and motivation for social contact were investigated at different time points, up to 29–36 days, after cessation of PCP treatment. During a social separation test, performed at 5 and 36 days, PCP treated rats spent less time near the divider that separates them from their familiar cage mate compared with saline (SAL) treated rats. Further, at short term, PCP was able to induce a decrease in social behavior. In contrast, at long-term, PCP treated animals spent more time in contact when exposed to an unfamiliar partner as compared to SAL treated rats. But, this difference was not observed when exposed to a familiar partner. We did not find any difference in ultrasonic vocalizations at all time points. The results of our study indicate that PCP is unable to induce overt long term deficits in social interaction behavior. Rather, it seems that PCP diminishes motivation for social contact. The long-term consequences of chronic PCP administration on social behavior in rodent models remain complex, and future studies addressing this are still needed. [ABSTRACT FROM AUTHOR]

Sexually naïve male C57BL/6 mice aggressively bite unfamiliar pups. This behavior, called infanticide, is considered an adaptive reproductive strategy of males of polygamous species. We recently found that the rhomboid nucleus of the bed nucleus of the stria terminalis (BSTrh) is activated during infanticide and that the bilateral excitotoxic lesions of BSTrh suppress infanticidal behavior. Here we show that 3-week-old male C57BL/6 mice rarely engaged in infanticide and instead, provided parental care toward unfamiliar pups, consistent with observations in rats and other rodent species. This inhibition of infanticide at the periweaning period is functional because the next litter will be born at approximately the time of weaning of the previous litter through maternal postpartum ovulation. However, the mechanism of this age-dependent behavioral change is unknown. Therefore, we performed whole-cell patch clamp recordings of BSTrh and compared evoked neurotransmission in response to the stimulation of the stria terminalis of adult and 3-week-old male mice. Although we were unable to detect a significant difference in the amplitudes of inhibitory neurotransmission, the amplitudes and the paired-pulse ratio of evoked excitatory postsynaptic currents differed between adult and 3-week-old mice. These data suggest that maturation of the synaptic terminal in BSTrh that occurred later than 3 weeks after birth may mediate by the adaptive change from parental to infanticidal behavior in male mice. [ABSTRACT FROM AUTHOR]

Cognitive bias tests measure variation in emotional appraisal and are validated methods to assess animals’ affective states. However, the link between social behaviours and cognitive bias has not yet been investigated. Bottlenose dolphins are a gregarious species for whom welfare research is increasing in importance, and thus are a good model to test such an association. We adapted a spatial location judgement bias test for eight captive bottlenose dolphins to investigate the link between cognitive bias and social behaviour, where we conducted behavioural observations outside of training sessions and did not experimentally induce an affective state. Subjects showed stable individual differences in cognitive biases across the three test days. Furthermore, dolphins showing more synchronous swimming, a fundamental affiliative behaviour, judged ambiguous cues significantly more optimistically. Our longer-term data showed cognitive bias and synchronous swimming frequency were significantly associated for up to two months preceding the test, but disappeared prior to that, suggesting that here cognitive bias differences were reflected by transitory affective states rather than longer-term traits. We hypothesise that the frequency of synchronous swimming may induce affective states and/or be induced by them; either way, it has strong potential as an indicator of affective state in this species and beyond. [ABSTRACT FROM AUTHOR]

Fragile X Syndrome (FXS) is a pervasive developmental disorder due to a mutation in the FMR1 X-linked gene. Despite its clear genetic cause, the expression of FXS symptoms is known to be modulated by environmental factors, including stress. Furthermore, several studies have shown disturbances in stress regulatory systems in FXS patients and Fmr1 mice. These studies have mostly focused on the hormonal responses to stress, using the acute exposure to a single type of stressor. Hence, little is known about the behavioral effects of stress in FXS, and the importance of the nature of the stressing procedure, especially in the context of a repeated exposure that more closely resembles real life conditions. Here we evaluated the effects of chronic exposure to different types of stress (i.e., either repeated restraint or unpredictable stress) on the behavioral phenotype of adult Fmr1 mice. Our results demonstrated that chronic stress induced deficits in social interaction and working memory only in WT mice and the impact of stress depended on the type of stressors and the specific behavior tested. Our data suggest that the behavioral sensitivity to stress is dramatically reduced in FXS, opening new views on the impact of gene-environment interactions in this pathology. [ABSTRACT FROM AUTHOR]

Moderate exposure to alcohol during development leads to subtle neurobiological and behavioral effects classified under the umbrella term fetal alcohol spectrum disorders (FASDs). Alterations in social behaviors are a frequently observed consequence of maternal drinking, as children with FASDs display inappropriate aggressive behaviors and altered responses to social cues. Rodent models of FASDs mimic the behavioral alterations seen in humans, with rats exposed to ethanol during development displaying increased aggressive behaviors, decreased social investigation, and altered play behavior. Work from our laboratory has observed increased wrestling behavior in adult male rats following prenatal alcohol exposure (PAE), and increased expression of GluN2B-containing NMDA receptors in the agranular insular cortex (AIC). This study was undertaken to determine if ifenprodil, a GluN2B preferring negative allosteric modulator, has a significant effect on social behaviors in PAE rats. Using a voluntary ethanol exposure paradigm, rat dams were allowed to drink a saccharin-sweetened solution of either 0% or 5% ethanol throughout gestation. Offspring at 6–8 months of age were implanted with cannulae into AIC. Animals were isolated for 24 h before ifenprodil or vehicle was infused into AIC, and after 15 min they were recorded in a social interaction chamber. Ifenprodil treatment altered aspects of wrestling, social investigatory behaviors, and ultrasonic vocalizations in rats exposed to ethanol during development that were not observed in control animals. These data indicate that GluN2B-containing NMDA receptors in AIC play a role in social behaviors and may underlie alterations in behavior and vocalizations observed in PAE animals. [ABSTRACT FROM AUTHOR]

Numerous animal species display behavioral changes in response to changes in social status or territory possession. For example, in male European starlings only males that acquire nesting sites display high rates of sexual and agonistic behavior. Past studies show that mu and delta opioid receptors regulate behaviors associated with social ascension or defeat. Opioids also act at kappa receptors, with dynorphin binding with the highest affinity; however, the role of these opioids in social behavior has not been well studied. We observed flocks of male starlings during the breeding season and ran quantitative real-time polymerase chain reaction (qPCR) to measure expression of kappa opioid receptors (OPRK1) and prodynorphin (PDYN) in brain regions involved in social behavior and motivation (ventral tegmental area [VTA], medial preoptic nucleus [mPOA]) and vocal behavior (Area X). Males with nesting territories displayed more sexual/agonistic behavior than males without nesting territories. They also had lower OPRK1 expression in VTA and mPOA. OPRK1 expression in VTA correlated negatively with sexual/agonistic behaviors, consistent with past studies showing kappa receptors in VTA to inhibit sociosexual behaviors. PDYN in mPOA correlated negatively with a measure of nesting behavior that may also reflect sexual motivation. PDYN in Area X related positively to song. Distinct patterns of OPRK1 and PDYN expression in VTA, mPOA, and Area X related to gonad volume, suggesting that breeding condition may modify (or be modified by) OPRK1 and PDYN expression. Studies are now needed to further characterize the role of OPRK1 and PDYN in status-appropriate social behaviors. [ABSTRACT FROM AUTHOR]

Chronic social behavior problems after pediatric traumatic brain injury (TBI) significantly contribute to poor quality of life for survivors. Using a well-characterized mouse model of early childhood TBI, we have previously demonstrated that young brain-injured mice develop social deficits by adulthood. As biological sex may influence both normal and aberrant social development, we here evaluated potential sex differences in post-TBI psychosocial deficits by comparing the behavior of male and female mice at adulthood (8 weeks post-injury). Secondly, we hypothesized that pediatric TBI would influence neuronal morphology identified by Golgi-Cox staining in the hippocampus and prefrontal cortex, regions involved in social cognition and behavior, before the onset of social problems (3 weeks post-injury). Morphological analysis of pyramidal neurons in the ipsilateral prefrontal cortex and granule cells of the hippocampal dentate gyrus revealed a reduction in dendritic complexity after pediatric TBI. This was most apparent in TBI males, whereas neurons from females were less affected. At adulthood, consistent with previous studies, TBI males showed deficits in sociability and social recognition. TBI females also showed a reduction in sociability, but intact social recognition and increased sociosexual avoidance. Together, these findings indicate that sex is a determinant of regional neuroplasticity and social outcomes after pediatric TBI. Reduced neuronal complexity in the prefrontal cortex and hippocampus, several weeks after injury in male mice, appears to precede the subsequent emergence of social deficits. Sex-specific alterations in the social brain network are thus implicated as an underlying mechanism of social dysfunction after pediatric TBI. [ABSTRACT FROM AUTHOR]

Despite continued study on the neurobiological bases of aggressive and sexual behaviors, it is still not well understood how the brain integrates social information with physiological and neural states to produce context-specific behavioral outcomes. In fishes, manipulation of endogenous levels of arginine vasotocin (AVT) through peripheral and intracerebroventricular pharmacological injections results in significant changes in social behaviors, including aggressive and reproduction-related behaviors. In addition, many features of AVT neurons have been shown to correlate with social status and associated behavioral phenotypes. In this study, we used the immediate early gene egr-1 as a marker for neuronal activity and quantified the number of AVT neurons that were positive for egr-1 mRNA by in situ hybridization in Astatotilapia burtoni males that were exposed to either a social context that would elicit aggression or to one that would elicit courtship. In these social settings, focal males readily displayed context- appropriate bouts of aggression (towards the opponent) or bouts of courting (towards females). We found that males that fought had higher levels of egr-1 expression in the preoptic area compared to courting males. A greater proportion of AVT cells was positive for egr-1 after a fight than after a bout of courting. We mapped mRNA distribution of AVT V1a receptor subtypes v1a1 and v1a2 in the brain and identified overlapping areas of expression in nuclei in the ventral telencephalon, hypothalamus and thalamus as key areas for AVT signaling in males. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is characterized by deficits in social communication and repetitive behaviors/restricted interests. One mouse model of ASD is the BTBR T+ Itpr tf /J (BTBR) mice which display low levels of social behavior in several tests. The social approach test is used to examine the preference for social interaction between a stranger mouse or a novel object. While female BTBR mice have been used in the social approach test, no one has examined the degree to which the strain of the stranger mouse will affect social behavior. The current experiment tested female BTBR subject mice in the social approach test with stranger mice from different strains including the BTBR, 129S1/SvImJ (129), and C57BL/6J (B6) mice, of which the B6 mice are most social. The results show that female BTBR mice overall spent significantly more time in the stranger mouse chamber. However, further analysis revealed that the subject mice spent significantly more time in the stranger mouse chamber when the stranger was from the B6 strain, but not the BTBR or 129 strains. The BTBR female mice also sniffed the B6 and 129 stranger mice more than the novel object. This suggests that BTBR females are more social with mice that display high levels of social behavior, but less so with less social mice. [ABSTRACT FROM AUTHOR]

Chronic social defeat has been found to be stressful and to affect many aspects of the brain and behaviors in males. However, relatively little is known about its effects on females. In the present study, we examined the effects of repeated social defeat on social approach and anxiety-like behaviors as well as the neuronal activation in the brain of sexually naïve female Mongolian gerbils (Meriones unguiculatus). Our data indicate that repeated social defeats for 20 days reduced social approach and social investigation, but increased risk assessment or vigilance to an unfamiliar conspecific. Such social defeat experience also increased anxiety-like behavior and reduced locomotor activity. Using ΔFosB-immunoreactive (ΔFosB-ir) staining as a marker of neuronal activation in the brain, we found significant elevations by social defeat experience in the density of ΔFosB-ir stained neurons in several brain regions, including the prelimbic (PL) and infralimbic (IL) subnuclei of the prefrontal cortex (PFC), CA1 subfields (CA1) of the hippocampus, central subnuclei of the amygdala (CeA), the paraventricular nucleus (PVN), dorsomedial nucleus (DMH), and ventrolateral subdivision of the ventromedial nucleus (VMHvl) of the hypothalamus. As these brain regions have been implicated in social behaviors and stress responses, our data suggest that the specific patterns of neuronal activation in the brain may relate to the altered social and anxiety-like behaviors following chronic social defeat in female Mongolian gerbils., Competing Interests: Declaration of Competing Interest The authors declare that there is no potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Adolescents exhibit great sensitivity to nicotine and social interaction; accordingly, when both stimuli are presented together, they interact to enhance the incentive value of the context in which they occur. Noteworthy, most studies assessing the interaction between nicotine and social reward have used isolated-reared rats. Adolescent isolation is an adverse condition that impacts brain development and behavior, so it is not known if the interaction also occurs in rats without social deprivation. The present study used a conditioned place preference model (CPP) to examine the interaction between nicotine and social reward in group-reared male adolescent rats. At weaning, Wistar rats were randomly assigned to four groups: vehicle, vehicle and a social partner, nicotine (0.1 mg/Kg s.c.), and nicotine and a social partner. Conditioning trials occurred on eight consecutive days followed by a test session in which the preference change was assessed. Besides the establishment of CPP, we examined the effects of nicotine on (1) social behaviors during CPP trials and (2) tyrosine hydroxylase (TH) and oxytocin (OT) as markers of changes in the neuronal mechanisms for reward and social affiliation. Similar to previous results, the joint presentation of nicotine and social reward induced CPP, whereas either nicotine or social interaction presented alone did not. This finding coincided with an increase in TH levels observed after nicotine administration only in socially conditioned rats. The interaction between nicotine and social reward is not related to the effects of nicotine on social investigation or social play., Competing Interests: Conflict of interest The authors do not have any conflicts of interest to report in connection with this manuscript., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Social stressors negatively impact social function, and this is mediated by the amygdala across species. Social defeat stress is an ethologically relevant social stressor in adult male rats that increases social avoidance, anhedonia, and anxiety-like behaviors. While amygdala manipulations can mitigate the negative effects of social stressors, the impact of social defeat on the basomedial subregion of the amygdala is relatively unclear. Understanding the role of the basomedial amygdala may be especially important, as prior work has demonstrated that it drives physiological responses to stress, including heart-rate related responses to social novelty. In the present study, we quantified the impact of social defeat on social behavior and basomedial amygdala neuronal responses using anesthetized in vivo extracellular electrophysiology in adult male Sprague Dawley rats. Socially defeated rats displayed increased social avoidance behavior towards novel Sprague Dawley conspecifics and reduced time initiating social interactions relative to controls. This effect was most pronounced in rats that displayed defensive, boxing behavior during social defeat sessions. We next found that socially defeated rats showed lower overall basomedial amygdala firing and altered the distribution of neuronal responses relative to the control condition. We separated neurons into low and high Hz firing groups, and neuronal firing was reduced in both low and high Hz groups but in a slightly different manner. This work demonstrates that basomedial amygdala activity is sensitive to social stress, displaying a distinct pattern of social stress-driven activity relative to other amygdala subregions., Competing Interests: Conflict of Interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Autism spectrum disorder (ASD) is a complicated, heterogeneous disorder characterized by social interaction deficits and repetitive stereotypical behaviors. Neuroinflammation and synaptic protein dysregulation have been implicated in ASD pathogenesis. Icariin (ICA) has proven to exert neuroprotective function through anti-inflammatory function. Therefore, this study aimed to clarify the effects of ICA treatment on autism-like behavioral deficits in BTBR mice and whether these changes were related to modifications in the hippocampal inflammation and the balance of excitatory/inhibitory synapses. ICA supplementation (80 mg/kg, once daily for ten days, i.g.) ameliorated social deficits, repetitive stereotypical behaviors, and short-term memory deficit without affecting locomotor activity or anxiety-like behaviors of BTBR mice. Furthermore, ICA treatment inhibited neuroinflammation via decreasing microglia number and the soma size in the CA1 region of the hippocampus, as well as the protein levels of proinflammatory cytokines in the hippocampus of BTBR mice. In addition, ICA treatment also rescued excitatory-inhibitory synaptic protein imbalance by inhibiting the increased vGlut1 level without affecting the vGAT level in the BTBR mouse hippocampus. Collectively, the observed results indicate that ICA treatment alleviates ASD-like features, mitigates disturbed balance of excitatory-inhibitory synaptic protein, and inhibits hippocampal inflammation in BTBR mice, and may represent a novel promising drug for ASD treatment., Competing Interests: Declaration of Competing Interest These authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pair bonding in humans and other socially monogamous species can have positive effects on health and well-being. These attachments also come with the potential for challenges such as separation, jealousy, or grief. Much of the work on the neurobiology of pair bonding in non-human primates has been carried out in coppery titi monkeys (Plecturocebus cupreus), a monogamous South American monkey, although these studies have been primarily in males. In the current study, we utilized female titi monkeys to experimentally examine responses to their monogamous male partner vs. a male stranger or being alone. Positron emission tomography (PET) scans were performed on eight adult female titi monkeys from well-established pairs. We used a within-subjects design in which each female underwent three different conditions after the fluorodeoxyglucose F 18 (FDG) injection: a) the subject was reunited with her partner, b) encountered a stranger, or c) was alone in the experimental cage. Behavioural observations were recorded, and plasma assayed for cortisol. Females housed alone showed higher cortisol compared with either the partner or stranger conditions. FDG uptake was higher in the amygdala and hippocampus when interacting with the stranger than the partner. Proximity modulated the relationship between social condition and FDG uptake in several areas. Females entered into mutual proximity more frequently with the partner than with the stranger. Female titi monkeys have different physiological, neural, and behavioural reactions to being with their partner, a stranger male, or being alone., Competing Interests: Declarations of interest The authors have no conflicts of interest to report., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)