Neurochemical Mediation of Affiliation and Aggression Associated With Pair-Bonding

Abstract

Background The neuropeptides vasopressin (AVP) and corticotrophin-releasing hormone (CRH) facilitate while serotonin (5-HT) inhibits aggression. How the brain is wired to coordinate interactions between these functionally opposed neurotransmitters to control behavioral states is poorly understood. Methods Pair-bonded male prairie voles (Microtus ochrogaster) were infused with a retrograde tracer, fluorogold, and tested for affiliation and aggression toward a female partner or novel female. Subsequent immunocytochemical experiments examined neuronal activation using FOS and neuro-chemical/-receptor profiles on brain areas involved in the behaviors. Finally, a series of behavioral pharmacological and real-time in-vivo brain microdialysis experiments were performed on male prairie voles displaying affiliation or aggression. Results We localized a subpopulation of excitatory AVP neurons in the anterior hypothalamic nucleus (AH) that may gate CRH output from the amygdala to the AH and then the lateral septum to modulate aggression associated with mate guarding. Conversely, we identified a subset of inhibitory 5-HT-ergic projection neurons in the dorsal raphe nucleus to the AH that mediates the spatio-temporal release of neuropeptides and their interactions in modulating aggression and affiliation. Conclusions Together, this study establishes the medial extended amygdala as a major neural substrate regulating the switch between positive and negative affective states wherein several neurochemicals converge and interact to coordinate divergent social behaviors.

A single prolonged stress paradigm produces enduring impairments in social bonding in monogamous prairie voles

“…Together with these reports, our results imply the involvement of a serotonin system in the formation of pair bond in prairie voles. This idea is consistent with a very recent report indicating that a subset of inhibitory serotonergic neurons projecting to the anterior hypothalamus mediate spatiotemporal release of neuropeptides in modulating affiliation [51]. …”

μ opioid receptor, social behaviour and autism spectrum disorder: reward matters

“…Remarkably, most of the former are well‐known key players of the reward system, such as dopamine, noradrenaline, cannabinoids, oxytocin or opioids (Dolen et al , ; Coria‐Avila et al , ; Baribeau and Anagnostou, ; Loureiro et al , ; Vanderschuren et al , ), and have been initially identified as neurochemical mediators of the motivational/rewarding properties of drugs of abuse and/or as pain killers. In contrast, neurobiological substrates of social avoidance [social avoidance systems (SAS)] have been characterized as main factors of the pain, aggression or stress systems and include 5‐HT, glucocorticoids and neuropeptides such as corticotropin‐releasing factor, arginine vasopressin, substance P or cholecystokinin (Katsouni et al , ; Takahashi et al , ; Barik et al , ; Katsouni et al , ; Gobbroge et al , ). Pro‐social and anti‐social neuromodulators thus compete to drive adaptive social behaviour in individuals.…”

The ties that bond: neurochemistry of attachment in voles

“…Novel semi-naturalistic field studies in prairie voles has found that DNA variation in the V1aR gene includes polymorphisms that predict the epigenetic status and neuronal expression of V1aR in a spatial memory circuit and this genomic diversity in V1aR is favored by selection [59 •• ] . Finally, our most recent data reveal neurochemical interactions between AVP, serotonin (5-HT), and CRH, in a neuronal microcircuit, encoding a male prairie vole’s decision to affiliate or fight his female partner or a stranger female [60 •• ] . Together with previous studies, the prairie vole field is ripe for incorporating contemporary molecular genetic tools like genomic tract-tracing, opto/chemo-genetic approaches, and gene editing via CRISPR technology.…”