In rats of both sexes, mating stimulates neuronal activity in forebrain areas that are also activated by stress. Hypothalamic cells in the arcuate (ARC) and paraventricular (PVN) nuclei synthesize hormones or peptides whose levels are altered by adrenalectomy. In this experiment, we examined whether the mating-induced expression of c-fos in the forebrain is altered by adrenalectomy (Adx) in female rats. Ovariectornized females were adrenalectomized (Adx) or sham-operated (Sham), hormone-primed and mated 2 weeks after surgery. They received 15 intromissions (151), 5 intromissions (51) or 15 mounts without intromission (MO) from a male or were taken directly from their home cage (HC). Two hours after mating, rats were perfused with paraformaldehyde and their brains were collected and stained immunocytochemically for FOS protein. FOS-immunoreactive (FOS-IR) cells in the posterodorsal medial amygdala (MePD), bed nucleus of stria terminalis (BNST), ventromedial hypothalamus (VMH), medial preoptic area (mPOA), ARC and PVN were counted bilaterally. In Sham animals, intromissions produced significant increases in FOS above HC levels. In Adx animals, mating increased FOS activity in all areas. However, responses to 51 and 151 differed between Sham and Adx groups. In all areas, Shams showed either the highest FOS response following 151 or levels which were equivalent after 51 and 151. In Adx animals, the greatest number of FOS-positive cells occurred after,51, with the 151 group showing significant suppression of FOS below 51 levels in the VMH, mPOA, ARC and PVN. These results demonstrate that the adrenal modulates FOS responses to mating in the female rat and suggest that adrenal secretory products normally may decrease sensitivity to low levels of mating stimulation. These effects may be due to increased corticotropin-releasing hormone (CRH) or P-endorphin in the hypothalamus after adrenalectomy Copyright (C) 2003 S. Karger AG, Basel.