Beyond serum testosterone: Sexual experience delays the decline of sexual behavior and preserves cellular density in...

Testosterone (T) modulates male sexual behavior, partly through actions in the medial preoptic area (mPOA) of the anterior hypothalamus. Although gonadectomy (GDX) rapidly depletes circulating T, the decline in sexual behavior is gradual, taking weeks or months. In some species, prior sexual experience delays this behavioral decay; however, whether this occurs in rats remains unclear. Here, we examined the effects of GDX and prior sexual experience on serum T levels, sexual behavior, and mPOA cellular density in male Wistar rats. Males were assigned to one of two groups: sexually experienced (Stud; n = 6) or naïve (Naïve; n = 6). Stud males underwent five 90-min copulatory sessions with receptive females at 4-day intervals, whereas naïve males were exposed to the chamber alone. All males were then gonadectomized and tested for T levels and sexual behavior at multiple time points from GDX: -1, + 1, + 7, + 30, + 45, and + 110. Sexual motivation was assessed using an olfactory preference test (urine from receptive vs. non-receptive females), and copulatory behavior was evaluated during encounters with receptive females. On GDX + 111, brains were collected for Nissl staining, and mPOA cell counts were quantified. Serum T decreased from approximately 10 ng/mL on GDX -1 to undetectable levels by GDX + 1 in all animals. Olfactory preference for receptive urine was decreased by GDX + 1, but not by + 7. On GDX + 45, stud males showed more genital investigations, mounts, and intromissions, as well as shorter latencies to mount and intromit, than naïve males; however, these differences were no longer evident by GDX + 110. Importantly, mPOA cell density was significantly higher in stud compared to naïve males. Thus, although GDX rapidly eliminates circulating T, prior sexual experience delays the decline of sexual motivation and behavior and is associated with increased cellular density in the mPOA. These findings contribute to understand that sexual experience induces neuroplastic changes in the mPOA that confer resilience to hormonal depletion.