Involvement of dorsal raphe nucleus serotonergic systems in social approach-avoidance behaviour and in the response to fluoxetine treatment in peri-adolescent female BALB/c mice

Abstract

Serotonergic systems are involved in the development and regulation of social behaviour, and drugs that target serotonin neurotransmission, such as selective serotonin reuptake inhibitors (SSRIs), also alter aspects of social approach-avoidance. The midbrain dorsal raphe nucleus (DR), which is a major serotonergic nucleus and main source of serotonergic innervation of the forebrain, has been proposed as an important target for SSRIs, although evidence in females is lacking. In this study, we examined the involvement of the DR serotonergic systems in social behaviour and in response to SSRI treatment, using peri-adolescent female BALB/c mice. Mice were exposed to the SSRI fluoxetine either chronically (18 mg/kg/day, in drinking water, for 12 days) or acutely (18 mg/kg, i.p.), or to vehicle control condition (0.9 % saline, i.p.), prior to being exposed to the three-chambered sociability test. Activation of serotonergic neurons across subregions of the DR were subsequently measured, using dual-label immunohistochemistry for TPH2 and c-Fos. Acute fluoxetine administration increased generalised and social avoidance, while mice exposed to chronic fluoxetine treatment showed levels of social approach behaviour that were comparable to controls. Serotonergic populations across the DR showed reduced activity following acute fluoxetine treatment. Further, activation of serotonergic neurons in the ventral DR correlated with social approach behaviour in vehicle-treated control mice. These data provide some support for the involvement of discrete populations of DR serotonergic neurons in the regulation of social approach-avoidance, although more research is needed to understand the effects and mechanisms of chronic SSRI treatment in females.