Effect of gonadectomy and hormone replacement on habenula-induced dopamine inhibition in female and male rats.

Sex differences have been noted in the prevalence and severity of several neurological and mental health disorders. Midbrain dopaminergic activity is implicated in the etiology of many of these disorders and therefore may also contribute to some commonly seen sex differences in presentation and treatment. The ability of the lateral habenula to inhibit midbrain dopamine firing activity is reduced in female rats, and we test here the hypothesis that circulating gonadal hormones contribute to this sex difference. In vivo, single unit, extracellular recordings of dopamine neurons were conducted in female and male rats that were intact, gonadectomized, or had hormone replacement. Both spontaneous and habenula-evoked activities were recorded. In accordance with previous findings, we found that habenular stimulation produces profound inhibition in dopamine neurons that is of longer duration in male rats than female rats. There was no effect of gonadectomy on duration of inhibition in either males or females. Although there was a trend toward stronger rebound excitation in control male rats, there was no significant effect of gonadectomy in either the male or female rats. Here we show that circulating gonadal hormones have no apparent effect on habenular evoked dopamine inhibition. We discuss the limitations of the current study, including the possibility that the influence of circulating gonadal hormones may be limited to sub-populations of midbrain dopamine neurons.