DREADD-Induced Inhibition of the Medial Amygdala and Ventromedial Nucleus of the Hypothalamus Affects Experience-Induced Enhancement of Paced Mating Behavior in Female Rats.

The acquisition of sexual experience leads female rats to return to the male more quickly after intromissions, receive intromissions at a faster rate, spend more time with the male during mating, and exhibit more proceptive behaviors during paced mating tests, suggesting heightened sexual motivation. Brain areas critical for sexual experience-enhanced paced mating behavior are unknown. Here, designer receptors exclusively activated by designer drugs (DREADDs) were used to test the hypothesis that silencing the medial amygdala (MeA) or ventromedial nucleus of the hypothalamus (VMH) across four paced mating tests would disrupt not only the display of paced mating behavior but also the enhancement of mating with sexual experience. Sexually naïve, ovariectomized rats received bilateral infusion into the MeA or VMH of a viral vector containing the gene for an inhibitory G-protein-coupled receptor (hM4Di) 3 weeks before behavioral testing. Rats were hormone primed with estradiol benzoate + progesterone and received either 1 mg/kg i.p. clozapine n-oxide (CNO) or vehicle 30 min before each of four 15-intromission tests of paced mating behavior. CNO given to rats lacking DREADD infusions did not exhibit disruptions to paced mating behavior. CNO-induced inhibition of the MeA altered paced mating behavior beginning with the first test, pointing to a role for the MeA in sensory processing of sexual stimulation. In contrast, inhibition of the VMH only led to changes in paced mating behavior on Tests 2-4, indicating that neural plasticity is induced in the VMH by sexual experience.