Sex Steroid Hormone Receptor Content of Medial Preoptic Efferents to the Ventral Tegmental Area Is Sexually Dimorphic: Implications for Sex Differences in Mesolimbic Reward Processing

Abstract

<b><i>Introduction:</i></b> The medial preoptic area (mPOA) is an important regulator of natural and drug-induced reward. However, despite the mPOA being implicated in sexually dimorphic reward responses, sex differences in medial preoptic efferents to the ventral tegmental area (VTA) have not been fully investigated. <b><i>Methods:</i></b> Two cohorts of male and female rats received unilateral injections of the tract-tracer Fluoro-Gold (FLG) into the VTA. Immunohistochemical staining was used to quantify co-labeled FLG-positive neurons with γ-aminobutyric acid (GABA), estrogen receptor α (ERα), and androgen receptors (AR). <b><i>Results:</i></b> Results revealed a pattern of VTA innervation that was comparable between males and females; more efferents emerged from the rostrocentral portions of the mPOA than caudal portions. Results also indicated that males and females had the same percentage of GABAergic mPOA-VTA projections. Differences emerged when investigating the hormone receptor profile of projections to the VTA, where females had a greater percentage of efferents expressing ERα and males had a greater percentage of efferents expressing AR, in the central portion of the mPOA. Lastly, FLG-positive cells were colocalized with GABA and ERα in cohort 1 and GABA and AR in cohort 2. The majority of AR-expressing cells colocalized with GABAergic efferents to the VTA, but only a portion of ERα-expressing cells colocalized with GABAergic efferents to the VTA. <b><i>Conclusion:</i></b> Results indicate that sex differences are present in the sex-steroid hormone receptor content of mPOA-VTA projections, particularly among efferents arising from the central region of the mPOA. These sexually dimorphic connections may influence a wide range of sex differences in reward responses.