Genotype differences in behavior and tyrosine hydroxylase expression between wild-type and progesterone receptor knockout mice.

Progesterone receptor (PR) activation can modulate the expression of male sexual behavior, both acutely in adulthood as well as during development, through long lasting effects on neural differentiation. One mechanism by which PR activation may affect behavior, during either epoch of life, is through alterations of the dopaminergic system. We investigated the effects of PR deletion on the sensitivity of sexual behavior to dopamine antagonism in male wild-type (WT) and progesterone receptor knockout (PRKO) mice and found that WT mice were more behaviorally sensitive to the effects of dopamine D1 receptor blockade. There were also genotype differences in tyrosine hydroxylase-immunoreactivity (TH-ir) in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) as well as genotype differences in how TH expression changed in response to social and sexual experience. In particular, in the VTA, sexually experienced PRKO mice had significantly more cells expressing TH than sexually experienced WT mice. In the SNc, experienced PRKO males had significantly more cells expressing TH than naive PRKO males. Thus, it appears that PR deletion affects the display of sexual behavior and its modulation by dopamine, as well as the differentiation of dopaminergic cells and the plasticity of those cells in response to social environment and behavioral experience.