ICV testosterone induces Fos in male Syrian hamster brain

Abstract

Previous studies in our laboratory have demonstrated intracerebroventricular (ICV) self-administration of testosterone in hamsters. This suggests that androgens are reinforcing, independent of their anabolic effects. Furthermore, pharmacologic testosterone acts as a depressant: ICV testosterone infusion acutely reduces respiration, locomotion and body temperature. However, with chronic exposure, males develop tolerance. To understand mechanisms for androgen action, we looked for Fos expression after acute and chronic ICV infusion of testosterone or vehicle. 32 castrated males with chronic physiologic testosterone replacement (n=8/group) were infused ICV for 4h/day with 40 microg testosterone or 40 microl vehicle. Half of the males were perfused after the first day of ICV infusion; the remaining males were perfused after 15 days of ICV infusion. 60 microm coronal brain slices were cut. Every fourth section was stained for Fos. Additional sections were stained for androgen receptors (AR) and estrogen receptors (ER). Testosterone infusion induced Fos above control in the posteromedial bed nucleus of the stria terminalis (BSTPM), posteromedial amygdala (MeP), lateral habenula (LHb), median raphe (MnR), lateral pontine nucleus (Pn), and ventral tegmental area (VTA). In particular, Fos was elevated in the BSTPM, MeP, LHb, and VTA only after 1 day of testosterone. 15 days of testosterone enhanced Fos expression above control in the MnR and lateral Pn. Importantly, Fos was not present in all brain areas involved in reward or in those with dense steroid receptors. Furthermore, AR and ER immunostaining was unaltered by testosterone infusion. We conclude that pharmacologic testosterone activates select steroid-sensitive brain regions, as well as midbrain areas involved in reinforcement of commonly-abused drugs.