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Whole-organism performance, including locomotor activity, is an important fitness trait in many animals. Locomotor activity is often classified into sprint speed and locomotor endurance and differences in sprint speed and locomotor endurance affect on other traits such as life-history traits. Previous studies found that locomotor endurance, sprint speed and brain dopamine (DA) levels are correlated with artificial selection for death feigning (an anti-predator behaviour that we refer to as 'death-feigning syndrome') in some insect species. Thus, if the syndrome has a genetic basis, death feigning, sprint speed and brain DA levels may be affected by artificial selection for locomotor endurance. We artificially selected for locomotor endurance over 10 generations in the red flour beetle Tribolium castaneum, and established higher (H) and lower activity (L) strains, then compared their death-feigning behaviour, sprint speed and brain DA levels. H-strain beetles exhibited significantly shorter duration of death-feigning, and significantly higher sprint speeds, suggesting variation in death-feigning syndrome. Surprisingly, although brain DA expression affects various animal behaviours, we found no significant differences in the brain DA expressions of H- and L-strain beetles. Thus, our results imply genetic correlations between locomotor endurance, sprint speed and death feigning, but not with brain DA expression, suggesting that differences in the biogenic amine results of our and previous studies may reflect differences in behavioural expression mechanisms.

OBJECTIVE: A substantial number of sexual assault victims report experiencing some form of peritraumatic tonic immobility (TI). A self-report questionnaire that is widely used to assess TI retrospectively is the Tonic Immobility Scale (TIS). This study explored the factor structure of the TIS in a clinical sample of adolescent and young adults.METHOD: The sample comprised 131 female rape victims, aged 13-25, who were referred for specialized trauma-focused treatment. An exploratory factor analysis (EFA) was performed.RESULTS: The EFA showed support for a three-factor model, with factors TI, Fear, and Detachment. Item correlations ranged from .32 to .57 for TI, from .14 to .35 for Fear, and .29 for the two Detachment items.CONCLUSIONS: We found support for a three-factor solution distinguishing TI, fear, and detachment, suggesting the need to further develop the TIS with different subscales in varying age groups and clinical samples. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background We recently showed that a neurosteroid analogue, (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH), induced hypnosis in rats. The aim of the present study was to evaluate the hypnotic and anaesthetic potential of 3β-OH further using electroencephalography. Methods We used behavioural assessment and cortical electroencephalogram (EEG) spectral power analysis to examine hypnotic and anaesthetic effects of 3β-OH (30 and 60 mg kg−1) administered intraperitoneally or intravenously to young adult male and female rats. Results We found dose-dependent sex differences in 3β-OH-induced hypnosis and EEG changes. Both male and female rats responded similarly to i.p. 3β-OH 30 mg kg−1. However, at the higher dose (60 mg kg−1, i.p.), female rats had two-fold longer duration of spontaneous immobility than male rats (203.4 [61.6] min vs 101.3 [32.1] min), and their EEG was suppressed in the low-frequency range (2–6 Hz), in contrast to male rats. Although a sex-dependent hypnotic effect was not confirmed after 30 mg kg−1 i.v., female rats appeared more sensitive to 3β-OH with relatively small changes within delta (1–4 Hz) and alpha (8–13 Hz) bands. Finally, 3β-OH had a rapid onset of action and potent hypnotic/anaesthetic effect after 60 mg kg−1 i.v. in rats of both sexes; however, all female rats and only half of the male rats reached burst suppression, an EEG pattern usually associated with profound inhibition of thalamocortical networks. Conclusions Based on its behavioural effects and EEG signature, 3β-OH is a potent hypnotic in rats, with female rats being more sensitive than male rats.

Posttraumatic stress disorder (PTSD) is a prevalent and disabling multisystem disorder, with significant physical and psychiatric morbidity and poor quality of life (QOL). Although peritraumatic reactions - tonic immobility and dissociation - are established predictors of PTSD severity and development, there is a dearth of investigation assessing the impact of peritraumatic reactions on QOL of PTSD patients. Quality of life has become increasingly important in health care and research as a reliable outcome measure. It comprises psychological, physical, social and environmental domains, providing important information about the impact of diseases on patient's life. This study aims to investigate the impact of peritraumatic tonic immobility and peritraumatic dissociation on QOL of PTSD civilian outpatients.It is a cross-sectional study of 50 victims of urban violence with current PTSD, recruited in a specialized outpatient clinic. Instruments used were: Structured Clinical Interview IV, Peritraumatic Dissociative Experiences Questionnaire, Tonic Immobility Scale and WHOQOL-BREF (psychological, physical, social and environmental domains). Linear regression models were fitted to evaluate the impact of peritraumatic reactions - tonic immobility and dissociation - on WHOQOL-BREF scores. We controlled for sex as potential confounding.The severity of peritraumatic tonic immobility negatively impacted on psychological and environment domains of quality of life. For each additional point on the Tonic Immobility Scale, there was a decreased of 0.8 points on the scores of these domains of WHOQOL-BREF. Neither the peritraumatic reactions showed effects on physical nor social domains. Possible limitations of this study include cross-sectional design, relatively small sample size of tertiary center outpatients and recall bias.Peritraumatic tonic immobility is related to poor quality of life, adding new insights about the relationship between this immobility reaction and PTSD.

The ability to escape predation modulates predator–prey interactions and represents a crucial aspect of organismal life history, influencing feeding, mating success, and survival. Thanatosis, also known as death feigning or tonic immobility (TI), is taxonomically widespread, but understudied in blood-feeding vectors. Hematophagous arthropods, such as ticks, are unique among animals as their predators (birds, mice, lizards, frogs, and other invertebrates) may also be their source of food. Therefore, the trade-off between predator avoidance and host-seeking may shift as the time since the last bloodmeal increases. Because ticks are slow-moving and unable to fly, or otherwise escape, we predicted that they may use TI to avoid predation, but that TI would be influenced by time since the last bloodmeal (starvation). We therefore aimed to quantify this relationship, examining the effect of starvation, body mass, and ontogeny on TI for two tick species: Dermacentor variabilis (Say) (Acari: Ixodidae) and Rhipicephalus sanguineus (Latreille) (Acari: Ixodidae). As we predicted, the duration and use of TI decreased with time since feeding and emergence across species and life stages. Therefore, ticks may become more aggressive in their search for a bloodmeal as they continue to starve, opting to treat potential predators as hosts, rather than avoiding predation by feigning death. Antipredator behaviors such as TI may influence the intensity and amount of time ticks spend searching for hosts, driving patterns of tick-borne pathogen transmission. This identification and quantification of a novel antipredation strategy add a new component to our understanding of tick life history.

Threatening stimuli challenging animal homeostasis are the primary events triggering defensive responses, including TI. The stress-response system (allostasis) is signaled by increased corticosteroid basal levels. In bird animal lines genetically selected for stress-induced corticosterone, there is a covariation between stress physiology and coping styles. Rabbit studies, in which the effects of TI are dissociated from those of induction per se, support the view that TI takes part in the homeostatic stress-response system. An increase of corticosterone is recorded just after the end of the induction procedure but not in the corresponding groups in which induction is followed by TI, suggesting a recovery process during TI. Similarly to corticosterone but in opposite direction, testosterone plasma levels decrease following induction and recover during TI. Recovery mechanisms are also suggested in two bird genotypes selected for long and short TI duration. The positive relation between corticosterone levels and TI duration has been confirmed after exogenous corticosterone administration.

In this conclusive chapter, we review findings giving support to the hypothesis that TI represents an adaptive, survival response to threatening situations. In models of prey-predator interactions, in vertebrates and invertebrates, there are evidence that immobility per se contributes to survival, as the predator loses interest for a prey in which TI is experimentally induced. TI duration is also reciprocally modulated by the evaluation of the risk factors in the environment, and by the opportunity to reach a safe refuge. This supports the adaptive value of TI and suggests that, during TI, the animal may be transiently aware of the environmental situation. As for the adaptive value of TI, genetic correlations with other behavioral systems contributing to fitness (e.g., mating) are taken into account. Moreover, neurophysiological and endocrine findings in mammals support our hypothesis that TI activates the mechanisms responsible for recovery from disruptive experiences and body lesions.

Animal models of autonomic correlates of defense behavior range from fish to mammals. There is however no study reporting heart and respiratory rate, blood pressure and body temperature simultaneously recorded in the same animal in association to different forms of immobility in response to threat: freezing, restraint-sustained immobility and tonic immobility (TI). In a prey/ predator context freezing behavior is associated with bradycardia and no change in blood pressure but in other conditions (e.g., extreme stressful stimuli) may be associated with tachycardia and hypertension. Restraint-sustained immobility does not affect blood pressure but may reduce heart rate according to the type of stimulus and mechanical pressure. Blood pressure and heart rate oscillate during TI induction and adjust at basal levels during TI, sometimes gradually decreasing below basal levels. In conclusion, in all these passive defense responses, the immobility is not due to a blood pressure collapse.

Modulation of Tonic Immobility (TI) concerns environmental and individual factors. TI is modulated by processes of habituation and sensitization. In poikilotherm frog and lizard, TI duration is much shorter at usual environmental temperatures and is potentiated at higher or lower temperatures, as the last resource for survival. During ontogeny, age may differentially affect TI susceptibility to the induction procedures, as in the case of newborn ectothermic and older endothermic rabbits. TI duration displays a daily rhythm, with longer TI in the night. Its resistance to habituation indicates that in the dark TI is the most prominent defense against nocturnal predators. In all studied species, there is synchronization of the prey's defensive responses with the feeding activity of predators. Ecological factors and exposure to different anthropogenic environmental pressures may alter morphology, behavior and TI in wild populations. TI duration has been associated with a genomic region comprising the dystrophin gene on quail chromosome 1.

In previous chapters, the available theories and experimental findings related to animals' defense responses have been reported and discussed in detail. This chapter reports their comprehensive synthesis, considering the main immobility-related responses in defense. Within the same modality (i.e., immobility) different kinds of immobility may in fact correspond to different functions and motivations, as proved by their neurobiological correlates profile.

This chapter summarizes the main neurophysiological characteristics of tonic immobility (TI), in many susceptible species of mammals and birds. During TI, cortical EEG shows high voltage slow waves whose amount is affected by events preceding TI induction and is positively correlated with TI duration. The pattern of hippocampal activity helps to predict TI onset and TI termination. Both polysynaptic flexor and monosynaptic heteronymous reflexes are depressed independently from the EEG activity. Brain metabolism, signaled by glycogen mobilization and glucose utilization, indicates a reduced neuronal activity during TI. Learned avoidance responses to shock can be extinguished during TI and recover after TI. Moreover, during TI animals may learn how to avoid the shock by a motor response that may be followed by TI interruption. Decortication, decerebellation and telencephalic sections do not affect TI characteristics, whereas ponto-mesencephalic sections abolish both righting reflexes and TI.

The genetic architecture of innate fear behavior in chickens is poorly understood. Here, we performed quantitative trait loci (QTL) analysis of innate responses to tonic immobility (TI) and open field (OF) fears in 242 newly hatched chicks of an F2 population between the native Japanese Nagoya breed and the White Leghorn breed using 881 single nucleotide polymorphism markers obtained by restriction site-associated DNA sequencing. At genome-wide 5% significance levels, four QTL for TI traits were revealed on chromosomes 1-3 and 24. Two of these loci had sex-specific effects on the traits. For OF traits, three QTL were revealed on chromosomes 2, 4 and 7. The TI and OF QTL identified showed no overlaps in genomic regions and different modes of inheritance. The three TI QTL and one OF QTL exerted antagonistic effects on the traits. The results demonstrated that context-dependent QTL underlie the variations in innate TI and OF behaviors.

β-hydroxybutyrate, a ketone body metabolite, has been shown to suppress depression-like behavior in rodents. In this study, we examined its antidepressive property in acute and chronic administration modes in mice by using forced swim test and tail suspension test. Results showed that the decrease effect of β-hydroxybutyrate (300 mg/kg) on immobility time in the tail suspension test and forced swim test in stress-naive mice began to be significant at day 11. In a dose-dependent experiment, β-hydroxybutyrate treatment (11 days) showed significant antidepressant activities at the dose of 200 and 300 mg/kg. Unlike fluoxetine, β-hydroxybutyrate treatment (300 mg/kg) showed no antidepressant activities in the acute (1 hour before the test) and three times administration mode within 24 hours (1, 5, and 24 hours before the test). But in a co-administration mode, β-hydroxybutyrate (100 mg/kg) -fluoxetine (2.5 mg/kg) co-administration exhibited an obvious antidepressant activity in the tail suspension test and forced swim test. Further analysis showed that the antidepressant effects of β-hydroxybutyrate and fluoxetine were not associated with the change in mouse locomotor activity. Furthermore, both chronic β-hydroxybutyrate treatment and β-hydroxybutyrate-fluoxetine co-treatment suppressed chronic unpredictable stress-induced increase in immobility time in the tail suspension test and forced swim test as well as chronic unpredictable stress-induced decrease in mouse body weight. Taken together, these results indicate that β-hydroxybutyrate (1) needs a relatively long time to show comparable behavioral activity to that of fluoxetine in assays that are sensitive to the behavioral effects of established antidepressant compounds and (2) can augment the antidepressant action of a sub-therapeutic dose of fluoxetine.

Background: Tonic immobility (TI; a state of motor arrest during threat) and has been found to be associated with the development of psychopathology. It also hindered recovery from posttraumatic stress disorder (PTSD) after pharmacological treatment. The present study investigated the role of TI in recovery from PTSD in a large representative community sample with mixed traumas outside an exclusive treatment context.Methods: Participants with PTSD from the panel for Longitudinal Internet Studies for the Social Sciences (LISS) completed measures for trauma, PTSD symptoms, and peritraumatic responses (fear, dissociation, and TI) in two subsequent years. Traumatized participants with PTSD were selected for the analyses (N = 262).Results: TI was a relevant predictor for increased PTSD symptoms in year 2 after controlling for peritraumatic fear, peritraumatic dissociation, and PTSD symptoms in year 1, especially in abuse victims. Peritraumatic fear and dissociation no longer predicted PTSD in year 2 after entering TI in the model.Conclusions: Our results indicate that TI may indeed hinder recovery from PTSD. TI may thus be a relevant factor to take into account after trauma and in treatment. The effects of TI may be especially negative for abuse victims.

The Coronavirus Disease 2019 (COVID-19) pandemic has exposed healthcare workers (HCW) to traumatic situations that might lead to the development of posttraumatic stress disorder (PTSD). An important vulnerability factor for PTSD is the peritraumatic tonic immobility (TI) reaction, an involuntary and reflexive defensive response evoked by an intense and inescapable threat. TI is largely understudied in humans and has not been investigated during trauma related to COVID-19. For HCW, the pandemic context might be experienced as an intense and potentially inescapable threat, i.e., an overwhelming situation. Here, we investigated if TI response occurred during traumatic events related to the pandemic and its association with posttraumatic stress symptoms (PTSS). An online survey of 1001 HCW investigated COVID-19-related traumatic experiences, TI and PTSS. TI was reported for all types of traumatic events, and multivariate regression models revealed that TI was significantly associated with PTSS severity. HCW who reported high TI scores exhibited an increase of 9.08 times the probability of having a probable diagnosis of PTSD. Thus, TI was evoked by pandemic-related traumatic situations and associated with PTSS severity and higher odds of a PTSD diagnosis. Tonic immobility occurrence should be screened, and psychoeducation about its reflexive biological nature should be introduced.

Predator avoidance is an important behavior that affects the degree of adaptation of organisms. We compared the DNA variation of one of the predator-avoidance behaviors, the recently extensively studied "death-feigning behavior", between the long strain bred for feigning death for a long time and the short strain bred for feigning death for a short time. To clarify how the difference in DNA sequences between the long and short strains corresponds to the physiological characteristics of the death-feigning duration at the transcriptome level, we performed comprehensive and comparative analyses of gene variants in Tribolium castaneum strains using DNA-resequencing. The duration of death feigning involves many gene pathways, including caffeine metabolism, tyrosine metabolism, tryptophan metabolism, metabolism of xenobiotics by cytochrome P450, longevity regulating pathways, and circadian rhythm. Artificial selection based on the duration of death feigning results in the preservation of variants of genes in these pathways in the long strain. This study suggests that many metabolic pathways and related genes may be involved in the decision-making process of anti-predator animal behavior by forming a network in addition to the tyrosine metabolic system, including dopamine, revealed in previous studies.

The dorsal immobility response (DIR) and the tonic immobility response (TIR) are cutaneo-motor reflexes typically triggered when a prey is seized. The neurochemical basis of the DIR appears to pass through the basal ganglia via dopaminergic fibers, while the neurochemical basis of the TIR appears to include a circuit comprising the amygdala, the periaqueductal gray (PAG), the dorsal raphe, and the nucleus magnus raphe (NMR) via glutamatergic, serotonergic, cholinergic, GABAergic, and opioid fibers. For the DIR, the basal ganglia also seem to be involved in regard to estradiol, while for the TIR, the HPA axis appears involved at the level of the amygdala and the oral pontine reticular nucleus.

Questions: Does advice from a physiotherapist about the importance of staying physically active during hospitalisation improve activity, mobility, strength, length of stay, and complications in older inpatients? What barriers to physical activity during hospitalisation do older inpatients perceive? Design: Randomised controlled trial with concealed allocation, intention-to-treat analysis, and blinded assessment. Participants: Sixty-eight people who were aged > 60 years and admitted to a university hospital ward. Intervention: In addition to usual hospital care, the experimental group received a booklet with content about the deleterious effects of hospitalisation and the importance of staying active during hospitalisation. The control group received usual hospital care only. Outcome measures: The amount of physical activity was measured via accelerometry during the hospital admission. Mobility was assessed using the de Morton Mobility Index (DEMMI), and muscle strength was assessed using a handgrip dynamometer. Length of stay and complications were extracted from hospital records. The barriers to staying active during hospitalisation were investigated via a questionnaire. Results: Accelerometry showed a mean between-group difference of 974 steps/day (95% CI 28 to 1919) in favour of the experimental group. The intervention also increased moderate-intensity physical activity and reduced sedentary time, although these effects might be trivially small. Experimental group participants were about one-fifth as likely to lose mobility during their hospital admission (two of 33) than control group participants (10 of 35), relative risk 0.21 (95% CI 0.05 to 0.90). Effects of the intervention were unclear regarding muscle strength, length of stay and incidence of complications between the groups. Patients reported that the main barriers to remaining active during hospitalisation were dyspnoea, lack of space, and fear of contracting infection. Conclusion: In older inpatients, the addition of advice from a physiotherapist about maintaining activity during hospitalisation increases the level of physical activity and prevents loss of mobility. Registration: ClinicalTrials.gov NCT03297567. Key words: Elderly, Hospitalisation, Immobility, Exercise, Accelerometry

Reduction of natural illumination in fall/winter months causes seasonal affective disorders (SAD) in vulnerable individuals. Neurotransmitter serotonin (5-HT) is involved in the mechanism of SAD. Tryptophan hydroxylase-2 (TPH2) is the key enzyme of 5-HT synthesis in the brain. C1473 G polymorphism in the Tph2 gene is a key factor defining the enzyme activity in the mouse brain. The main aims of the study were to investigate the effects of C1473 G polymorphism on behavior and brain 5-HT system responses to photoperiod alterations. The experiment was carried out on adult mouse males of B6-1473C and B6-1473 G congenic lines with normal and low TPH2 activities, respectively. B6-1473C and B6-1473 G mice were divided into four groups of 8 each and exposed for 28 days to standard-day (14 h light and 10 h darkness) or short-day (4 h light and 20 h darkness) conditions. No effect of photoperiod on locomotor, exploratory activities and anxiety in the open field test was observed. At the same time, photoperiod alterations affected depressive-like immobility in the forced swim test, the 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) levels, 5-HIAA/5-HT ratio and the Htr2a mRNA level in hippocampus and midbrain. The effect of the interaction between C1473 G polymorphism and photoperiod on 5-HT level and 5-HIAA/5-HT ratio in hippocampus was revealed. Short-day conditions reduced the level and increased 5-HIAA/5-HT ratio in this structure only in B6-1473 G mice. At the same time, C1473 G polymorphism does not alter effects of short-day conditions on immobility time in the forced swim test and the Htr2a mRNA level in the brain.

Fear is the emotion that is best understood in terms of brain mechanisms. And the management of fear memories is important when facing mental health disorders such as post-traumatic stress. Adolescence is a transitional stage of physical and psychological human development and the ability to deal with the fear memory in adolescence may be a potent factor for developing mental disorders in adulthood. However, little is known about the direct relationship between the ability to deal with the fear memory and appearance of depressive-like behaviors. To assess this, we used a model of associative learning to induce the fear memories and evaluated the depressive-related behaviors in the fear memory extinction process and its underlying cellular mechanisms from adolescent and adult mice. We found that, compared with adult mice, the adolescent mice exhibited impaired fear memory extinction in contextual fear conditioning extinction process. Meanwhile, impaired fear memory extinction was accompanied by more immobility time in forced swimming test, which was used to assess the depressive-like state. Consistent with this, we observed that long-term potentiation (LTP) induction in the hippocampal CA1 region of adolescent mice persistently larger in extinction process in adolescent mice, which was involved the presynaptic mechanism. Together, our results suggest that adolescent mice exhibited a disability to extinct the fear memory, and that this may lead to the depressive-like behaviors via presynaptic-mediated synaptic plasticity. These findings may give us a new insight in the knowledge of some mental disorders caused by persistent unpleasant memories.

Tonic immobility (TI) is a temporary state of profound motor inhibition associated with great danger as the attack of a predator. Previous studies carried out in our laboratory evidenced high Fos-IR in the posteroventral region of the medial nucleus of the amygdala (MEA) after induction of the TI response. Here, we investigated the effects of GABAA and GABAB of the MEA on TI duration. Intra-MEA injections of the GABAA agonist muscimol and GABAB agonist baclofen reduced TI response, while intra-MEA injections of the GABAA antagonist bicuculline and GABAB antagonist phaclofen increased the TI response. Moreover, the effects observed with muscimol and baclofen administrations into MEA were blocked by pretreatment with bicuculline and phaclofen (at ineffective doses per se). Finally, the activation of GABAA and GABAB receptors in the MEA did not alter the spontaneous motor activity in the open field test. These data support the role of the GABAergic system of the MEA in the modulation of innate fear.

ObjectivesNMDA antagonists and nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects and may represent treatment options for depression. The behavioural effects of NMDA antagonists seem to depend on Tyrosine kinase B receptor (TrkB) activation by BDNF and on mechanistic target of rapamycin (mTOR), in the medial prefrontal cortex (mPFC). However, it is unknown whether similar mechanisms are involved in the behavioural effects of NOS inhibitors. Therefore, this work aimed at determining the role of TrkB and mTOR signalling in the prelimbic area of the ventral mPFC (vmPFC-PL) in the antidepressant-like effect of NOS inhibitors.MethodsPharmacological treatment with LY235959 or ketamine (NMDA antagonists), NPA or 7-NI (NOS inhibitors), BDNF, K252a (Trk antagonist) and rapamycin (mTOR inhibitor) injected systemically or into vmPFC-PL followed by behavioural assessment.ResultsWe found that bilateral injection of BDNF into the vmPFC-PL induced an antidepressant-like effect, which was blocked by pretreatment with K252a and rapamycin. Microinjection of LY 235959 into the vmPFC-PL induced antidepressant-like effect that was suppressed by local rapamycin but not by K252a pretreatment. Microinjection of NPA induced an antidepressant-like effect insensitive to both K252a and rapamycin. Similarly, the antidepressant-like effects of a systemic injection of ketamine or 7-NI were not affected by blockade of mTOR or Trk receptors in the vmPFC-PL.ConclusionOur data support the hypothesis that NMDA blockade induces an antidepressant-like effect that requires mTOR but not Trk signalling into the vmPFC-PL. The antidepressant-like effect induced by local NOS inhibition is independent on both Trk and mTOR signalling in the vmPFC-PL.

The objective of the present study is to investigate the role of α4, α5, α6 or β2 nAChR subunits in the antidepressant-like effect of bupropion. Adult male mice were treated with subcutaneous acute doses of bupropion (3 and 10 mg/kg) 30 min before the forced swim test (FST) in α4, α5, α6, or β2 nAChR subunit knockout (KO) and wild-type (WT) mice. In addition, the effects of β2* antagonist dihydro-β-erythroidine (DHβE, 3 mg/kg) on antidepressant-like effects of bupropion in C57BL/6 J mice were assessed. Our results showed that baseline immobility and climbing time did not differ between KO and corresponding WT mice except for β2 KO. Bupropion significantly decreased immobility time and increased climbing time in the α4, α6 and β2 nAChR KO mice in comparison to WT littermates, indicating that lack of these nAChR subunits enhanced antidepressant effects of bupropion. On the contrary, the α5 nAChR subunit deletion did not alter the FST behavior in the bupropion-treated mice. Not only in the transgenic mice, bupropion also showed antidepressant-like effects in the WT mice. In addition, DHβE pretreatment before bupropion administration resulted in decreased immobility time and increased climbing time. Taken together, the present study provides evidence on the involvement of α4*, α6*, and β2* (* indicates possible presence of other subunits) nAChRs in the antidepressant-like effects of bupropion in the FST.

Accumulating evidence indicates that the antidepressant effects of ketamine are, in part, mediated by an increase in the AMPA receptor-mediated neurotransmission in depression related areas, such as the prefrontal cortex (PFC). Therefore, activity in PFC-projecting areas related to major depression, such as the dorsal raphe nucleus (DR), may also be modulated by ketamine. We used whole-cell patch-clamp recordings and western blot experiments to determine whether ketamine promotes acute and maintained alterations in glutamatergic transmission and mTOR pathway in the DR. Bath perfusion of ketamine, but not the NMDA receptor antagonist D-AP5, increased the frequency of AMPA receptor-mediated spontaneous EPSCs (sEPSCs) in DR neurons. However, ketamine did not affect evoked EPSCs or spontaneous inhibitory currents (sIPSCs). Pre-incubation of DR slices with the mTOR inhibitor PP242 decreased the frequency of sEPSCs and prevented the effect of ketamine. The results also show that while no electrophysiological effects were detected 24 h after ketamine administration, phosphorylation levels of mTOR were significantly increased in the DR. Nevertheless, expression levels of synaptic proteins were unaffected at that time. Altogether, the present data demonstrate that ketamine transiently increases spontaneous AMPA receptor-mediated neurotransmission in the DR.

Childhood absence epilepsy (CAE) is the most common pediatric epilepsy syndrome and is characterized by typical absence seizures (AS). AS are non-convulsive epileptic seizures characterized by a sudden loss of awareness and bilaterally generalized synchronous 2.5–4 Hz spike and slow-wave discharges (SWD). Gamma butyrolactone (GBL) is an acute pharmacological model of AS and induces bilaterally synchronous SWDs and behavioral arrest. Despite the long use of this model, little is known about its strain and sex-dependent features. We compared the dose-response profile of GBL-evoked SWDs in three rat strains (Long Evans, Sprague-Dawley, and Wistar), and examined the modulatory effects of estrous cycle on SWDs in female Wistar rats. We evaluated the number of seizures, the cumulative time seizing, and the average seizure duration as a function of dose, strain, and sex/estrous phase. Long Evans rats displayed the greatest sensitivity to GBL, followed by Wistar rats, and then by Sprague-Dawley rats. GBL-evoked SWDs were modulated by estrous cycle in female rats, with the lowest sensitivity to GBL occurring during metestrus. Wistar rats showed the greatest variability as a function of dose, and the least variability within dose; these features make this strain desirable for interventional studies. Moreover, our finding that the SWD response to GBL differs as a function of estrous cycle underscores the importance of cycle monitoring in studies examining female animals using this model. Together, these strain and sex-dependent findings provide guidance for future studies.

Although catatonia is related to several medical conditions, catatonia as a response to trauma and posttraumatic stress disorder (PTSD) is less clear. The aim of this review is to explore the small emerging body of preliminary evidence that suggests a possible correlation between psychological trauma and catatonia. Initial data suggests a correlation between episodes of intense fear associated with trauma and PTSD and some forms of catatonic responses. Although this relationship is still speculative to be causative, it can have important implications if confirmed. This is especially salient when it is examined alongside existing studies of the response to fear in animals and the phenomenon of tonic immobility, which bears a striking resemblance to catatonia in humans. If prospective studies further support the initial findings, it could change our conceptual understanding of the etiology of a subtype of catatonia substantially while pointing to likely targets of further research to understand the biological mechanisms that underlie the illness.

We investigated the anti-stress effect of rosemary (

BACKGROUND A group of diplegic cerebral palsied (CP) children presents six precise signs that can be easily observed during clinical examinations, physiotherapy sessions and everyday activities. These signs are: startle reaction, upper limbs in startle position, averted-eye gaze, grimaces, eye blinking and posture freezing. METHODS In a population of 32 diplegic CP children (aged 1-8 years) perceptual signs were retrospectively identified through videos to verify their stability in the same child over time. RESULTS Startle reaction, upper limb in startle position and posture freezing were the most frequently observed signs and the easiest to recognize with the highest agreement in both observations (P

BackgroundThe emerging line of research suggests that neuro-inflammation and oxidative stress are linked to the development of depression-like behavior. The tryptophan metabolizing enzyme, indolamine 2,3-dioxygenase (IDO), serves as an important interface between chronic inflammation and depression. IDO is induced by pro-inflammatory cytokines and diverts tryptophan towards the kynurenine pathway, decreasing serotonin synthesis. Further, the metabolites of kynurenine pathway increase brain oxidative stress and also cause N-methyl-D-aspartate (NMDA) receptor-mediated exitotoxicity. The resulting oxidative damage and dysfunction in glutamatergic neurotransmission alters the network connectivity of the brain, which may be the further mechanism for emergence of depression-like symptoms.MethodsA depression-like illness was induced in mice by injecting Bacillus Calmette-Guerin (BCG) suspended in isotonic saline at a dose of 107 CFU I.P. The mice were then divided into different groups and were administered MK-801 or normal saline for the next 21 days, after which a battery of behavior and biochemical tests were conducted to assess them.ResultsThe BCG group had significantly reduced sucrose preference index and an increase in immobility time in forced swim test (FST) and Tail Suspension Test (TST) as compared to the saline group. There was also a significant increase in the brain MDA levels and a decline in the brain GSH levels. The hippocampal tissue from the BCG group had significantly more comet cells than the saline group. The NMDA receptor antagonist, MK-801, was able to reverse the BCG-induced depression-like behaviour. MK-801 also showed significant decrease in brain oxidative stress but failed to show significant protection against BCG-induced neurotoxicity observed in comet assay.ConclusionsThe NMDA receptor antagonist, MK-801, mitigated BCG-induced, depressive-like behavior in mice by improving the sucrose preference and decreasing the duration of immobility time in TST and FST. The overall improvement in depression-like behavior was accompanied by a reduction in brain oxidative stress and comet cells, thus suggesting the antioxidant and neuroprotective action of MK-801.

The aim of this study was to investigate the differences in fearfulness between two Japanese native chicken breeds, Tosa-Kukin (TOK) and Yakido (YKD). In a tonic immobility test, TOK breed chicks showed longer duration and lower induction number compared with YKD. The number of peeps in YKD in an isolation test was lower than that in TOK, whereas there were more bouts of peeping in YKD than in TOK. In a manual restraint test, YKD showed more active responses and initiated peeps and struggling earlier than TOK. The three behavioral tests all indicated that YKD are less fearful than TOK chickens. A latent structures discriminant (OPLS-DA) analysis was used to identify behavioral parameters that contributed to the differences between the breeds. The major parameters were duration and number of inductions in the tonic immobility test and number of struggle in the manual restraint test. These results suggest that three behavioral tests can be used together to evaluate fearfulness of Japanese native breeds of chickens.

In the present study we have monitored dose dependent effects of midazolam; a benzodiazepine (CNS depressant). It is the primary drug of choice for procedural sedation, preoperative sedation, and in emergency departments. Repeated administration of this drug is reported to have abuse potential and may cause this by increasing dopaminergic neurotransmission. Since an important role of 5-hydroxy tryptamine (5-HT) is there in the pathophysiology of anxiety and addiction, administration of midazolam may involve altered 5-HT metabolism as well. Present study was designed to monitor dose-dependent effects of midazolam and select the optimum dose for further experiments. Effects of midazolam were monitored on food intake, growth rate, activities in familiar and novel environments, light dark box activity, hot plate test, forced swim test and levels of dopamine, 5-HT and their metabolites. Midazolam was administered orally (0mg/kg, 2.5mg/kg, 5.0mg/kg and 10mg/kg) and behaviors were monitored post single midazolam administrations. Rats were decapitated and whole brain samples were collected and stored at -70°C until neurochemical analysis by HPLC-EC. Findings from the present study could be implicated to increased therapeutic utility of midazolam and related benzodiazepines.

The lateral habenula (LHb) processes information about aversive experiences that contributes to the symptoms of stress disorders. Previously, we found that chemogenetic inhibition of rat LHb neurons reduced immobility in the forced swim test, but the downstream target of these neurons was not known. Using an intersectional viral vector strategy, we selectively transduced three different output pathways from the LHb by injecting AAV8-DIO-hM(4)Di into the LHb and CAV2-CRE (a retrograde viral vector) into one of the three target areas as follows: dorsal raphe nucleus (DRN), ventral tegmental area (VTA), or rostromedial tegmentum (RMTg). Using the forced swim test, we found that chemogenetic inhibition of DRN-projecting LHb neurons reduced passive coping (immobility), whereas inhibition of the other pathways did not. Chemogenetic activation of DRN-projecting neurons using hM3Dq in another cohort did not further exacerbate immobility. We next examined the impact of inhibiting DRN-projecting LHb neurons on reward sensitivity, perseverative behavior, and anxiety-like behavior using saccharin preference testing, reward-omission testing, and open-field testing, respectively. There was no effect of inhibiting any of these pathways on reward sensitivity, locomotion, or anxiety-like behavior, but inhibiting DRN-projecting LHb neurons reduced perseverative licking during reward-omission testing, whereas activating these neurons increased perseverative licking. These results support the idea that inhibiting LHb projections to the DRN provides animals with resilience during highly stressful or frustrating conditions but not under low-stress circumstances, and that inhibiting these neurons may promote persistence in active coping strategies.

Made available in DSpace on 2021-06-25T15:38:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 This study was carried out to estimate genetic parameters for morphology, body weight, and tonic immobility traits in the red-winged tinamou (Rhynchotus rufescens). Information on 690 birds was used and genetic parameters were estimated using Bayesian methods under a multi-trait animal model. The following traits were considered in this study: tarsal length (TL), bill length (BL), wing length (WL), head width (HW), bill width (BW), mature weight (MW), weight at 90 days (W90), and tonic immobility (TI). The heritability showed estimates between 0.15 for wing length and 0.56 for bill length. Positive and negative genetic correlations were estimated, ranging from - 0.33 to 0.81. All the morphological, production, and behavioral traits studied will have moderate to high response to selection. The body weight at 90 days is a better alternative for use in breeding programs and its selection would not lead to an increase in the time of tonic immobility. Both the selection for weight gain and for reduction of tonic immobility time would lead to an increase in the size of the legs of the red-winged tinamou, which could be advantageous for thermal control of these birds in tropical systems. State Univ Southwest Bahia, BR-45700000 Itapetinga, BA, Brazil Inst Fed Goiano, Campus Rio Verde,Km1,Cx Postal 66, BR-75901970 Rio Verde, Go, Brazil Univ Estadual Paulista, BR-14884900 Jaboticabal, SP, Brazil Fed State Univ Grande Dourados, BR-79825070 Dourados, MS, Brazil Univ Estadual Paulista, BR-14884900 Jaboticabal, SP, Brazil

Depression is the most common psychiatric disorder in diabetic patients, showing higher rates in women than in men. This comorbidity has been studied in rodents using the streptozotocin (STZ)-induced diabetes (DM) model, consistently reporting a depressive-like profile in males. Few articles have examined these disturbances in females (ovariectomized or combined with male rats) yielding controversial results. This work was aimed to study whether there are sex differences in the depressive-like profile of STZ-treated male and naturally cycling female Wistar rats. We also analyzed the possible influence of the estrous cycle in females. DM was induced by injecting STZ (50 mg/kg, i.p.) in 2 consecutive days. Ten days later, the depressive-like profile was assessed in the Forced-Swim Test (FST). Locomotion and motor coordination were also evaluated. Body weight and blood glucose levels were registered at the beginning and at the end of the experiment; the estrous cycle, food and water intake were daily monitored. All diabetic subjects showed increased blood glucose levels, polyphagia, polydipsia and decreased body weight as compared to controls, but males were more susceptible to STZ-treatment than females pooled in all phases of the estrous cycle. After treatment with STZ, males and females in proestrus/estrus (P/E) exhibited a depressive-like profile in the FST (increased immobility and reduced swimming); females in metestrus/diestrus were unaffected. The only sex difference observed was a more pronounced reduced swimming in STZ-treated P/E females compared with hyperglycemic males. No changes in locomotion or motor coordination were found. This work emphasizes estrous cycle differences in STZ-treated rats, and in the resultant depressive-like profile. It also supports clinical evidences made in women with DM and stresses the importance of studying STZ-treated naturally cycling females and their estrous cycle phases.

Scopolamine, a muscarinic cholinergic receptor antagonist, exerts fast and prolonged antidepressant effects in the clinic. In contrast, the current treatments for major depressive disorder (MDD) require long-term drug administration. On the other hand, the sole use of scopolamine might be related to the high risk of adverse effects. Therefore, it may be preferable to reduce its therapeutic dose. A new approach might include the co-administration of low-dose scopolamine with selected ligands of metabotropic glutamate (mGlu) receptors, which are known to possess antidepressant-like activity in several rodent tests and models of depression. The aim of the present study was to evaluate the potential antidepressant activity of low-dose scopolamine combined with an allosteric agonist of mGlu7 receptors, AMN082 in C57BL/6 mice. It was found that the combination of scopolamine (0.1 mg/kg) and AMN082 (1 mg/kg) exerted significant antidepressant-like effects in the tail suspension test (TST), but these effects were not observed in the mGlu7−/− mice. Furthermore, low-dose AMN082 co-administered with low-doses scopolamine (0.03 and 0.1 mg/kg) induced antidepressant-like activity in the forced swim test (FST) in mice. The tested compounds did not affect locomotor activity and did not impair spatial memory in the Morris water maze (MWM) test or motor coordination in the rotarod test. The results strongly indicated that there is an enhanced antidepressant-like action of scopolamine by AMN082. Co-administration of scopolamine with AMN082 might be a new strategy with better efficacy and a lower risk of adverse effects compared with the sole use of scopolamine or AMN082.

Tonic immobility (TI) is an innate defensive response exhibited by prey when physical contact with a predator is prolonged and inescapable. This defensive response is able to activate analgesia mechanisms; this activation has adaptive value because, during an attack by a predator, the manifestation of recuperative behaviors can affect the appropriate behavioral defense strategy. Some studies have suggested that similar structures of the central nervous system can regulate the response of both TI and nociception. Thus, this study evaluated the effect of chemical lesion through the administration of ibotenic acid in restricted brain areas of the periaqueductal gray matter (PAG) in guinea pig on the TI response and nociception evaluated in the hot plate test before and after emission of TI. The data showed that an irreversible chemical lesion in the ventrolateral PAG reduced of the TI response as well as defensive antinociception. However, a lesion in the dorsal PAG blocked the defensive antinociception induced by TI but did not alter TI duration. In summary, one could hypothesize that the neural substrates responsible for defensive behavior and antinociception represent similar systems that are distinct in modulation. Thus, the ventrolateral PAG has been associated with the modulation of TI and the defensive antinociception induced by TI. In contrast, the integrity of the dorsal PAG should be necessary for defensive antinociception to occur but not to elicit TI behavior in guinea pigs.

Considering the pivotal role of nitric oxide (NO) pathway in depressive disorders, the aim of the present study was to investigate the antidepressant-like effect of selegiline in mice forced swimming test (FST), and possible involvement of NO-cyclic guanosine monophosphate (cGMP) pathway in this action. After assessment of locomotor activity in open-field test, mice were forced to swim individually and the immobility time of the last 4 min was evaluated. All drugs were given intraperitoneally (ip). Selegiline (10 mg/kg) decreased the immobility time in the FST similar to fluoxetine (20 mg/kg). Pretreatment with l-arginine (NO precursor, 750 mg/kg) or sildenafil (a phosphodiesterase 5 inhibitor, 5 mg/kg) significantly reversed the selegiline anti-immobility effect. Sub-effective dose of selegiline (1 mg/kg) showed a synergistic antidepressant effect with NG-nitro-l-arginine methyl ester (L-NAME, inhibitor of NO synthase, 10 mg/kg) or 7-nitroindazole (specific neuronal NO synthase inhibitor, 30 mg/kg), but not with aminoguanidine (specific inducible NO synthase inhibitor, 50 mg/kg). Pretreatment of mice with methylene blue (an inhibitor of NO synthase and soluble guanylyl cyclase, 10 mg/kg) significantly produced a synergistic response with the sub-effective dose of selegiline. Neither of the drugs changed the locomotor activity. Also, hippocampal and prefrontal cortex (PFC) nitrite content was significantly lower in selegiline-injected mice compared to saline-administrated mice. Also, co-injection of 7-nitroindazole with selegiline produced a significant reduction in hippocampal or PFC nitrite contents. It is concluded that selegiline possesses antidepressant-like effect in mice FST through inhibition of l-arginine-NO-cyclic guanosine monophosphate pathway.

Numerous studies have attributed the psychopathology of anxiety and stress disorders to maladaptive behavioral responses such as an inability to extinguish fear. Therefore, understanding neural substrates of fear extinction is imperative for developing more effective therapies for anxiety and stress disorders. Although several studies indicated a role for cholinergic transmission and nicotinic acetylcholine receptors (nAChRs) in anxiety and stress disorder symptomatology, very little is known about the specific contribution of nAChRs in the fear extinction process. In the present study, we first examined the involvement of several brain regions essential for fear extinction (i.e., dorsal and ventral hippocampus, dHPC and vHPC; infralimbic, IL, and prelimbic, PL of the medial prefrontal cortex, mPFC; basolateral nucleus of the amygdala, BLA) in the impairing effects of a nAChR agonist, nicotine, on contextual fear extinction in mice. Our results showed that systemic administration of nicotine during contextual fear extinction increased c-fos expression in the vHPC and BLA while not affecting dHPC, IL or PL. In line with these results, local nicotine infusions into the vHPC, but not dHPC, resulted in impaired contextual fear extinction. Interestingly, we found that local nicotine infusions into the PL also resulted in impairment of contextual fear extinction. Second, we measured the protein levels of the GABA synthesizing enzymes GAD65 and GAD67 in the dHPC and vHPC during contextual fear extinction. Our results showed that in the group that received acute nicotine, both GAD65 and GAD67 protein levels were downregulated in the vHPC, but not in dHPC. This effect was negatively correlated with the level of freezing response during fear extinction suggesting that the downregulated GAD65/67 levels were associated with disrupted fear extinction. Finally, using c-fos/GAD65/67 double immunofluorescence, we showed that nicotine mainly increased c-fos expression in non-GABAergic ventral hippocampal cells, indicating that acute nicotine increases vHPC excitability. Overall, our results suggest that acute nicotine's impairing effects on fear extinction are associated with ventral hippocampal disinhibition. Therefore, these results further our understanding of the interaction between nicotine addiction and anxiety and stress disorders by describing novel neural mechanisms mediating fear extinction.

A single base mutation in the Gα(i2) protein (G184S) renders this Gα subunit insensitive to the negative modulatory effects of Regulator of G-protein Signaling (RGS) proteins. Mice expressing this RGS insensitive (RGSi) variant of Gα(i2) (RGSi Gα(i2)) display a spontaneous antidepressant-like phenotype that is reversible by treatment with the 5-HT1A receptor (5-HT1AR) antagonist WAY100635. Here we test the hypothesis that increased activity of 5-HT1ARs in the hippocampus of RGSi Gα(i2) knock-in mice is responsible for the expression of the observed antidepressant-like behavior. We administered the 5-HT1AR antagonist WAY100635 or the agonist 8-OH-DPAT via bilateral intra-hippocampal infusion cannulae and evaluated antidepressant-like behavior using the tail suspension test (TST). WAY100635 reversed the antidepressant-like phenotype of the RGSi Gα(i2) knock-in mice and 8-OH-DPAT produced an antidepressant-like response in wild type mice that was blocked by systemic WAY100635. Furthermore, intra-hippocampal infusion of the RGS4/19 inhibitor CCG-203769 produced an antidepressant-like effect in female mice. Ex-vivo slice recording confirmed the 5-HT1AR-mediated decrease in hippocampal CA1 pyramidal neuron excitability was enhanced in the RGSi Gα(i2) knock-in mice. There was no change in hippocampal 5-HT1AR expression as measured by ligand binding or in the ability of 8-OH-DPAT to activate G-protein as measured in the [(35)S]GTPγS binding assay. The findings demonstrate that RGS protein control of hippocampal 5-HT1AR signaling is necessary and sufficient to account for the antidepressant-like phenotype in the RGSi Gα(i2) knock-in mice and that RGS proteins highly expressed in the hippocampus should be investigated as targets for novel antidepressant therapies.

Rats emit 22 kHz ultrasonic vocalizations (USVs) in association with pain, fear, or distress. Whereas the capacity to produce USVs is innate, reactivity to them appears to require experience. Specifically, 22 kHz USVs fail to elicit freezing behavior in naive laboratory rats. However, these “alarm calls” do elicit freezing in rats that previously experienced foot shocks. These findings led to the hypothesis that acquired reactivity is based on “autoconditioning”—learning in which self-generated 22 kHz USVs serve as Pavlovian cues that become associated with foot shocks. The current study tested the autoconditioning hypothesis by devocalizing rats through a unilateral transection of the recurrent laryngeal nerve (Experimental group). Subsequently, animals in both the Experimental and sham-operated Control groups received five unsignaled foot shocks. One or two days later, both groups were tested for USV-elicited freezing in a novel context. Recurrent laryngeal nerve transection failed to prevent or even diminish USV-elicited freezing. In fact, both groups showed large and comparable increases in freezing to USV presentations. A subset of Control animals failed to vocalize during conditioning, while some Experimental animals did vocalize during conditioning. Animals were therefore re-grouped and reanalyzed based on whether they vocalized during conditioning. Again, both groups showed large and comparable increases in USV-elicited freezing. These results disconfirm the essential tenet or prediction of the autoconditioning hypothesis. Alternative mechanisms for acquired reactivity to 22 kHz USVs are therefore considered.

Stress exposure has been implicated in the development of mood disorders, although little is known about the lasting effects of repeated stress during the adolescent period on sex-specific differences in endocrine and plasticity-signaling responses in adulthood. Using a 10-day combinatory stress paradigm (postnatal day (PND) 26 to 35), we examined sex-specific impact of adolescent stress and inhibition of tyrosine-related kinase B (TrkB) receptor (ANA-12; 0.5 mg/kg, i.p.) on 1) adolescent blood corticosterone levels, 2) adult locomotion and anxiety-like behavior, and 3) region-specific differences in endogenous TrkB full-length (TrkB.FL) and truncated (TrkB.T1) receptor isoforms. Blood collected on days 1, 5 and 10 revealed elevated basal and stress-induced CORT secretion in females compared to males, while ANA-12 attenuated CORT elevations post stress in both sexes. As adults, all females exhibited higher locomotor and exploratory activity than males in the open field test and elevated plus maze, and differences were comparable in the forced swim within stress-naive and stress groups. Biochemically, vehicle-treated males showed elevated TrkB.T1 and TrkB.FL compared to vehicle-treated females in the PFC, hippocampus and NAc, and levels were consistently attenuated by ANA-12 treatment in non-stress males. With regards to stress exposure, expression of both isoforms was strongly down-regulated in the NAc of males only and was associated with increased TrkB.T1 in the PFC. ANA-12 enhanced expression in females, independent of stress exposure, compared to vehicle-treated counterparts, expression being increased for TrkB.T1 versus TrkB.FL and magnitude of the changes being region-specific. In contrast, ANA-12 effects in stressed males were restricted to inhibition of both isoforms in the hippocampus. Together, our findings support that TrkB activation, contingent on stress exposure, differentially affects TrkB isoform regulation during adulthood. Sex-specific biochemical responses at delayed intervals following adolescent stress exposure further support the need to include the sex variable in animal models.

Children with an extremely inhibited, anxious temperament (AT) are at increased risk for anxiety disorders and depression. Using a rhesus monkey model of early-life AT, we previously demonstrated that metabolism in the central extended amygdala (EAc), including the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST), is associated with trait-like variation in AT. Here, we use fMRI to examine relationships between Ce–BST functional connectivity and AT in a large multigenerational family pedigree of rhesus monkeys (n = 170 females and 208 males). Results demonstrate that Ce–BST functional connectivity is heritable, accounts for a significant but modest portion of the variance in AT, and is coheritable with AT. Interestingly, Ce–BST functional connectivity and AT-related BST metabolism were not correlated and accounted for non-overlapping variance in AT. Exploratory analyses suggest that Ce–BST functional connectivity is associated with metabolism in the hypothalamus and periaqueductal gray. Together, these results suggest the importance of coordinated function within the EAc for determining individual differences in AT and metabolism in brain regions associated with its behavioral and neuroendocrine components. SIGNIFICANCE STATEMENT Anxiety disorders directly impact the lives of nearly one in five people, accounting for substantial worldwide suffering and disability. Here, we use a nonhuman primate model of anxious temperament (AT) to understand the neurobiology underlying the early-life risk to develop anxiety disorders. Leveraging the same kinds of neuroimaging measures routinely used in human studies, we demonstrate that coordinated activation between the central nucleus of the amygdala and the bed nucleus of the stria terminalis is correlated with, and coinherited with, early-life AT. Understanding how these central extended amygdala regions work together to produce extreme anxiety provides a neural target for early-life interventions with the promise of preventing lifelong disability in at-risk children.

To better understand the role of gut microbiota in the anxiety, we isolated bifidobacteria and lactobacilli from the human faecal microbiota, investigated their inhibitory effects on the expression of interleukin (IL)-6 and tumour necrosis factor (TNF)-α in lipopolysaccharide-stimulated macrophages, and examined the anxiolytic-like effect of Bifidobacterium adolescentis IM38 in mice treated with or without immobilisation stress using the elevated plus maze (EPM) task. Oral administration of IM38 at a dose of 1×109 cfu/mouse showed a significant anxiolytic-like effect both in mice exposed to immobilisation stress and in control mice using the EPM test (PA receptor and modulate stress-related cytokine expression.

The importance of optimal early life conditions of broilers to sustain efficient and healthy production of broiler meat is increasingly recognized. Therefore, novel husbandry systems are developed, in which immediate provision of nutrition post hatch is combined with on-farm hatching. In these novel systems , 1-day-old-chick handling and transport are minimized. To study whether early nutrition and reduced transport are beneficial for broiler performance and behavior , the effects of early or delayed nutrition and post-hatch handling and transport were tested from hatch until 35 d of age, in a 2 × 2 factorial arrangement. In total, 960 eggs were hatched in 36 floor pens. After hatch, chicks were given immediate access to water and feed (early nutrition) or after 54 h (delayed nutrition). Eighteen hours after hatch, chicks remained in their pens (non-transported control), or were subjected to short-term handling and transport to simulate conventional procedures. Subsequently, chicks returned to their pens. Compared with delayed-fed chickens, early-fed chickens had greater body weight up to 21 d of age, but not at slaughter (35 d of age). No effects of transport or its interaction with moment of first nutrition were found on performance. At 3 d post hatch, transported , early-fed chicks had a greater latency to stand up in a tonic immobility test than transported, delayed-fed chicks, but only in chicks that were transported. At 30 d post hatch, however, latency was greater in transported, delayed-fed chickens than in transported, early-fed chicks. This may indicate long-term delete-rious effects of delayed nutrition on fear response in transported chickens. It is concluded that early nutrition has mainly beneficial effects on performance during the first 2 wk post hatch, but these beneficial effects are less evident in later life. The combination of transport and early nutrition may influence the chicken's strategies to cope with stressful events in early and later life.

One problem area regarding animal models for affective disorders is unclear reproducibility, including external validity or generalizability. One way to evaluate external validity is with systematic reviews and meta-analyses. The current study presents a meta-analysis of the effects of prototypic antidepressants in the mouse forced swim test (FST). We identified studies that examined effects of antidepressants in the FST in mice and used standard protocol, male mice and acute drug administration. We calculated Effect sizes using Cohen's d, homogeneity using Q statistic and correlations using Pearson's correlation. Results indicate that all drugs reduce immobility in the FST. However, effect sizes for most drugs are heterogeneous and do not show a consistent dose/response relationship across variability factors. Reducing variability by examining only one strain or data from individual laboratories partially increases dose response relationship. These findings suggest that whereas the FST is a valid tool to qualitatively screen antidepressant effects its validity in the context of hierarchical comparison between doses or compounds might be relevant only to single experiments.