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Shadani, S.

Publications and source records attributed to Shadani, S..

2 recordsLinked to original sources
bioRxiv2025

Psilocybin modulates social behaviour in male and female mice in a time-dependent manner

With the resurgence of psychedelic research and the growing interest in their therapeutic potential, there is an urgent need to understand how these compounds act across biological sexes. Despite widespread interest in their use for conditions marked by social impairments, including depression, anxiety, and anorexia nervosa, the influence of sex as a biological variable (SABV) on the prosocial effects of psychedelics remains poorly understood. Indeed, enhanced connectedness, sociability and empathy are common outcomes of psychedelic use and these have shaped human social structures for millennia. Here, we investigated the sex-specific effects of a single dose of psilocybin (1.5 mg/kg) in C57BL/6J mice on various aspects of social behaviours. We show an intriguing connection between huddling behaviour and body temperature acutely elicited by psilocybin that was restricted to females. We also observe temporally distinct patterns of social behaviour alterations in female mice, whereby enhanced preference for social novelty was observed after acute effects subsided (4 h post-administration), which was maintained for [~]24 h. Longer-term, the impact of psilocybin was reversed and promoted preference for familiar over novel conspecifics when assessed 7d post-administration, which was associated with prolonged nucleus accumbens dopamine signalling during familiar sniffing. In males, psilocybin reduced stress-related behaviours at 24 h and increased preference for familiar conspecifics, along with blunted novelty-evoked dopamine responses at both 24 h and 7 days post-treatment. Both 5-HT1A and 5-HT2A receptors were involved in modulating these behaviours, though in sex-specific ways. These findings highlight that the prosocial effects of psychedelics are not universal and emphasize the importance of sex-informed approaches in both preclinical research and clinical application. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/695064v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@5f9786org.highwire.dtl.DTLVardef@1d4e2b5org.highwire.dtl.DTLVardef@16ff7c3org.highwire.dtl.DTLVardef@1f32e33_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗
bioRxiv2025

Psilocybin exerts differential effects on social behaviour and inflammation in mice in contexts of activity-based anorexia (ABA)

Psychedelics, particularly psilocybin, have shown therapeutic potential across several psychiatric conditions, including depression, anxiety, obsessive-compulsive disorder, and anorexia nervosa (AN). These disorders often share social deficits that may be effectively alleviated by psychedelics considering their use has been linked with emotional empathy and enhanced social cognition. However, the mechanisms through which psychedelics alter social behaviour are unclear, and mechanistic studies in animal models have largely focused on male subjects. This is problematic for understanding the therapeutic effects relevant for disorders that predominantly affect females, such as AN. Here, we used the activity-based anorexia (ABA) mouse model to examine the effects of a single psilocybin dose on social behaviour in female mice and compared outcomes to mice exposed to food restriction (FR), exercise (RW) or standard housing (Controls). Together with these metabolic stressors, we also investigated the effects of psilocybin on the circulating proinflammatory cytokine interleukin-6 (IL-6), which is implicated in AN and is suppressed by psychedelics. Psilocybin did not alter sociability in ABA, RW, or FR mice but increased preference for familiarity in Controls. Novelty-seeking behaviour was elevated in both ABA and RW groups, although with distinct social patterns. Psilocybin elevated IL-6 levels in RW mice, which was positively correlated with preference for novelty. No such relationships were found in ABA or FR groups. These findings reveal subtle, context-dependent effects of psilocybin on social behaviour and inflammation in female mice, highlighting the need to clarify its temporal, neuroplastic, and immune-related mechanisms across sexes and disease models.

neuroscience↗