Sex-specific and social experience-dependent oxytocin–endocannabinoid interactions in the nucleus accumbens: implications for social behaviour

Abstract

Oxytocin modulates social behaviour across diverse vertebrate taxa, but the precise nature of its effects varies across species, individuals and lifetimes. Contributing to this variation is the fact that oxytocin's physiological effects are mediated through interaction with diverse neuromodulatory systems and can depend on the specifics of the local circuits it acts on. Furthermore, those effects can be influenced by both genetics and experience. Here we discuss this complexity through the lens of a specific neuromodulatory system, endocannabinoids, interacting with oxytocin in the nucleus accumbens to modulate prosocial behaviours in prairie voles. We provide a survey of current knowledge of oxytocin–endocannabinoid interactions in relation to social behaviour. We review in detail recent research in monogamous female prairie voles demonstrating that social experience, such as mating and pair bonding, can change how oxytocin modulates nucleus accumbens glutamatergic signalling through the recruitment of endocannabinoids to modulate prosocial behaviour toward the partner. We then discuss potential sex differences in experience-dependent modulation of the nucleus accumbens by oxytocin in voles based on new data in males. Finally, we propose that future oxytocin-based precision medicine therapies should consider how prior social experience interacts with sex and genetics to influence oxytocin actions. This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.

Developmental trajectory of social reward motivation from early adolescence into adulthood in female and male Long‐Evans rats

“…The oxytocinergic system also modulates social behavior, including social reward (Menon & Newman, 2023), and its receptor densities increase significantly in early adolescence and into adulthood (Hammock, 2015). Notably, oxytocin and endocannabinoids interact in the nucleus accumbens to influence social reward (Borie et al., 2022). Thus, this variety in trajectories of development of different neural systems and evidence of discontinuities in behavioral development during adolescence suggest that the variability in results obtained in investigations of adolescence may be based in variation in the ages involved across studies.…”

Acute, chronic and conditioned effects of intranasal oxytocin in the mu opioid receptor knockout mouse model of autism: social context matters

“…OT therefore appears to behave as a coincidence detector for social experience and reward processes, allowing the reinforcement of social interactions. The neuronal substrate of such action would involve striatal regions, notably D 1 R and D 2 R-SPNs in the NAc, and interaction with multiple neuromodulators [9, 88]. In mice exposed to OT concomitantly with social experience, we found Drd1a and Drd2 transcripts downregulated in the CPu, as well as in the NAc of Oprm1 +/+ and Oprm1 -/- mice for the former, and in the VP/Tu of Opmr1 null mice for the latter, pointing to modulation of dopaminergic transmission in these regions irrespective of genotype [89].…”

Tickling of rats is associated with positive affective states, but does not replicate juvenile social play regarding the involvement of central oxytocin and vasopressin systems

“…period. Future research should also investigate the interaction between the endocannabinoid or dopaminergic systems in response to tickling (reviewed in [ 32,59 ]) due to its rewarding aspects.…”