A role for the medial preoptic area in neuroendocrine modulation of sex differences in reward

The medial preoptic area (mPOA), located in the rostral hypothalamus, is an important regulator of motivated behaviors in rats. While its role in naturally rewarding behaviors, such as maternal care and sexual behavior, is well established, its role in drug response is just beginning to be explored. As a major site of neuroendocrine integration with direct connections to the mesolimbic dopamine system, it is not surprising that the mPOA is implicated in the modulation of sex differences in reward responses. Prior work has demonstrated that activation of the mPOA in response to sexual and parental reward differs between males and females, but whether sex differences are present in medial preoptic responses to drugs of abuse is unknown. Here, a role for the mPOA in the regulation of neuroendocrine-induced sex differences in neural and behavioral responses to cocaine is uncovered. Furthermore, while it is known that the mPOA influences the mesolimbic dopamine system through efferent connections with the ventral tegmental area (VTA), whether there are sex differences in the extent and profile of these projections remains unclear. The use of an iontophoretically injected tract-tracer, in conjunction with immunohistochemical techniques, revealed sex differences in mPOA efferents to the VTA. Specifically, projections from the central mPOA to the VTA contain more estrogen receptors and fewer androgen receptors in females, compared to males. Taken together, this work identifies the mPOA as a modulator of neuroendocrine-induced sex differences in downstream reward processing.