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Serotonin signaling plays critical roles in social and emotional behaviors. Likewise, decades of research demonstrate that the amygdala is a prime modulator of social behavior. Permanent excitotoxic lesions and transient amygdala inactivation consistently increase social behaviors in non-human primates. In rodents, acute systemic administration of drugs that increase serotonin signaling is associated with decreased social interactions. However, in primates, the direct involvement of serotonin signaling in the amygdala, particularly in affiliative social interaction, remains unexplored. Here, we examined the effects of serotonin manipulations within the amygdala on social behavior in eight pairs of familiar male macaques. We microinfused drugs targeting the serotonin system into either the basolateral (BLA) or central (CeA) amygdala and measured changes in social behavior. Surprisingly, the results demonstrated no significant differences in social behavior following the infusion of a selective serotonin reuptake inhibitor, 5-HT 1A agonist or antagonist, 5-HT 2A agonist or antagonist, or 5-HT 3 agonist or antagonist into either the BLA or CeA. These findings suggest that serotonin signaling in the amygdala does not directly contribute to the regulation of social behavior between familiar conspecifics. Future research should explore alternative mechanisms and potential interactions with other brain regions to gain a comprehensive understanding of the complex neural circuitry governing social behavior., Competing Interests: Declarations. Conflict of interests: The authors declare no competing financial interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Traumatic stress, particularly during critical developmental periods such as adolescence, has been strongly linked to an increased propensity and severity of aggression. Existing literature underscores that being a victim of abuse can exacerbate aggressive behaviors, with the amygdala playing a pivotal role in mediating these effects. Historically, animal models have demonstrated that traumatic stressors can increase attack behavior, implicating various amygdala nuclei. Building on this foundation, our previous work has highlighted how traumatic stress invokes long-lasting aggression via an excitatory pathway within the posterior ventral medial amygdala (MeApv). In the current study, we sought to further delineate this mechanism by examining the effects of acute social defeat during adolescence on aggressive behaviors and neural activation in mice. Using a common social defeat paradigm, we first established that acute social defeat during late adolescence indeed promotes long-lasting aggression, measured as attack behavior 7 days after the defeat session. Immunolabeling with c-Fos demonstrated that acute social defeat activates the MeApv and ventrolateral aspect of the ventromedial hypothalamus (VmHvl), consistent with our previous studies that used foot shock as an acute stressor. Finally, chemogenetically inhibiting excitatory MeApv neurons during social defeat significantly mitigated the aggression increase without affecting non-aggressive social behavior. These results strongly suggest that the MeApv plays a critical role in the onset of aggression following traumatic social experience, and offer the MeA as a potential target for therapeutic interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mojahed, Adjei, Qasem, Aaflaq, Adu, Jacobs, Richardson and Nordman.)

The nucleus accumbens (NAc) is a central component of the brain circuitry that mediates motivated behavior, including reward processing. Since the rewarding properties of social stimuli have a vital role in guiding behavior (both in humans and nonhuman animals), the NAc is likely to contribute to the brain circuitry controlling social behavior. In rodents, prior studies have found that focal pharmacological inhibition of NAc and/or elevation of dopamine in NAc increases social interactions. However, the role of the NAc in social behavior in nonhuman primates remains unknown. We measured the social behavior of eight dyads of male macaques following (1) pharmacological inhibition of the NAc using the GABA A agonist muscimol and (2) focal application of quinpirole, an agonist at the D2 family of dopamine receptors. Transient inhibition of the NAc with muscimol increased social behavior when drug was infused in submissive, but not dominant partners of the dyad. Focal application of quinpirole was without effect on social behavior when infused into the NAc of either dominant or submissive subjects. Our data demonstrate that the NAc contributes to social interactions in nonhuman primates., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Waguespack et al.)

Traumatic stress has been shown to contribute to persistent behavioral changes, yet the underlying neural pathways are not fully explored. Structural plasticity, a form of long-lasting neural adaptability, offers a plausible mechanism. To scrutinize this, we used the mGRASP imaging technique to visualize synaptic modifications in a pathway formed between neurons of the posterior ventral segment of the medial amygdala and ventrolateral segment of the ventromedial hypothalamus (MeApv-VmHvl), areas we previously showed to be involved in stress-induced excessive aggression. We subjected mice (7-8 weeks of age) to acute stress through foot shocks, a reliable and reproducible form of traumatic stress, and compared synaptic changes to control animals. Our data revealed an increase in synapse formation within the MeApv-VmHvl pathway post-stress as evidenced by an increase in mGRASP puncta and area. Chemogenetic inhibition of CaMKIIα-expressing neurons in the MeApv during the stressor led to reduced synapse formation, suggesting that the structural changes were driven by excitatory activity. To elucidate the molecular mechanisms, we administered the NMDAR antagonist MK-801, which effectively blocked the stress-induced synaptic changes. These findings suggest a strong link between traumatic stress and enduring structural changes in an MeApv-VmHvl neural pathway. Furthermore, our data point to NMDAR-dependent mechanisms as key contributors to these synaptic changes. This structural plasticity could offer insights into persistent behavioral consequences of traumatic stress, such as symptoms of PTSD and social deficits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bartsch, Jacobs, Mojahed, Qasem, Smith, Caldwell, Aaflaq and Nordman.)

Psilocybe zapotecorum is a strongly blue-bruising psilocybin mushroom used by indigenous groups in southeastern Mexico and beyond. While this species has a rich history of ceremonial use, research into its chemistry and genetics have been limited. Herein, we detail mushroom morphology and report on cultivation parameters, chemical profile, and the full genome sequence of P. zapotecorum . First, growth and cloning methods are detailed that are simple, and reproducible. In combination with high resolution microscopic analysis, the strain was barcoded, confirming species-level identification. Full genome sequencing reveals the architecture of the psilocybin gene cluster in P. zapotecorum, and can serve as a reference genome for Psilocybe Clade I. Characterization of the tryptamine profile revealed a psilocybin concentration of 17.9±1.7 mg/g, with a range of 10.6-25.7 mg/g (n=7), and similar tryptamines (psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, 4-HO-tryptamine, and tryptamine) in lesser concentrations for a combined tryptamine concentration of 22.5±3.2 mg/g. These results show P. zapotecorum to be a potent - and variable - Psilocybe mushroom. Chemical profiling, genetic analysis, and cultivation assist in demystifying these mushrooms. As clinical studies with psilocybin gain traction, understanding the diversity of psilocybin mushrooms will assure that psilocybin therapy does not become synonymous with psilocybin mushrooms.

Ketamine is a dissociative anesthetic that has been shown to have antidepressant effects in humans and has been proposed as a potential treatment for mood disorders such as posttraumatic stress disorder and aggression. However, previous studies from our lab and others have demonstrated that ketamine's effects are highly context- and dose-dependent. In a recent study, we found that 10 mg/kg ketamine could exacerbate the effects of early life stress on excessive aggression in mice. To further investigate, the effect of ketamine on moods, such as fear, anxiety, depression, and aggression, we used a mouse model of early life stress, involving chronic social isolation followed by acute traumatic stress in the form of noncontingent, unpredictable foot shock during adolescence. We find this is necessary to induce long-lasting excessive aggression in a novel environment. Seven- to eight-week-old socially isolated mice were given IP injections of 10 mg/kg ketamine 30 min before being subjected to foot shock and then assessed 7 days later for changes in sociability, aggression, mobility, anxiety-like behavior, and depression-like behavior. The results show that ketamine selectively increases long-lasting aggression in mice exposed to foot shock, but does not affect mood-related behaviors or locomotion. These findings suggest that during early life stress, ketamine may exert its effects by specifically targeting aggression brain circuitry that is distinct from brain circuits responsible for nonaggressive social or emotional behaviors. Therefore, while ketamine may be a promising treatment for various mood disorders, caution should be exercised when using ketamine to treat disorders associated with early life stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sensorimotor gating is the ability to suppress motor responses to irrelevant sensory inputs. This response is disrupted in a range of neuropsychiatric disorders. Prepulse inhibition (PPI) of the acoustic startle response (ASR) is a form of sensorimotor gating in which a low-intensity prepulse immediately precedes a startling stimulus, resulting in an attenuation of the startle response. PPI is conserved across species and the underlying circuitry mediating this effect has been widely studied in rodents. However, recent work from our laboratories has shown an unexpected divergence between the circuitry controlling PPI in rodents as compared to macaques. The nucleus accumbens, a component of the basal ganglia, has been identified as a key modulatory node for PPI in rodents. The role of the nucleus accumbens in modulating PPI in primates has yet to be investigated. We measured whole-body PPI of the ASR in six rhesus macaques following (1) pharmacological inhibition of the nucleus accumbens using the GABA A agonist muscimol, and (2) focal application of the dopamine D2/3 agonist quinpirole (at 3 doses). We found that quinpirole, but not muscimol, infused into the nucleus accumbens disrupts prepulse inhibition in monkeys. These results differ from those observed in rodents, where both muscimol and quinpirole disrupt prepulse inhibition., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The bed nucleus of the stria terminalis (BNST) has been implicated in a variety of social behaviors, including aggression, maternal care, mating behavior, and social interaction. Limited evidence from rodent studies suggests that activation of the BNST results in a decrease in social interaction between unfamiliar animals. The role of the BNST in social interaction in primates remains wholly unexamined. Nonhuman primates provide a valuable model for studying social behavior because of both their rich social repertoire and neural substrates of behavior with high translational relevance to humans. To test the hypothesis that the primate BNST is a critical modulator of social behavior, we performed intracerebral microinfusions of the GABA A agonist muscimol to transiently inactivate the BNST in male macaque monkeys. We measured changes in social interaction with a familiar same-sex conspecific. Inactivation of the BNST resulted in significant increase in total social contact. This effect was associated with an increase in passive contact and a significant decrease in locomotion. Other nonsocial behaviors (sitting passively alone, self-directed behaviors, and manipulation) were not impacted by BNST inactivation. As part of the "extended amygdala," the BNST is highly interconnected with the basolateral (BLA) and central (CeA) nuclei of the amygdala, both of which also play critical roles in regulating social interaction. The precise pattern of behavioral changes we observed following inactivation of the BNST partially overlaps with our prior reports in the BLA and CeA. Together, these data demonstrate that the BNST is part of a network regulating social behavior in primates. SIGNIFICANCE STATEMENT The bed nucleus of the stria terminalis (BNST) has a well-established role in anxiety behaviors, but its role in social behavior is poorly understood. No prior studies have evaluated the impact of BNST manipulations on social behavior in primates. We found that transient pharmacological inactivation of the BNST increased social behavior in pairs of macaque monkeys. These data suggest the BNST contributes to the brain networks regulating sociability., (Copyright © 2023 the authors.)

This study examined the differences in adherence to medication for the treatment of depressive mood disorders whether the patient was involved in split or integrated therapy and if the patient was being treated by a psychiatrist or an advanced practice registered nurse (APRNs) in psychiatry with prescriptive authority. The sample consisted of 122 adults ages 20-60 who carried a diagnosis of major depression, dysthymia, or bipolar II disorder, voluntarily treated in the private sector. Chi-square was the measure used to assess differences in adherence. Adherence was determined by documentation from chart reviews, retrospectively, of the prescriptions for psychotropic medication for a period of up to nine months for each patient included in the research. Six psychiatrists and six APRNs volunteered to collect data from their private practices. Findings demonstrated no statistically significant differences in patient's adherence to medication if they were in split or integrated treatment or if either psychiatrists or an APRN treated them. Psychiatrists used more of secondary class of antidepressants and more antianxiety agents than did the APRNs. The nurses spent more time with patients, using more integrated therapy, than did the psychiatrists.