Male preference for the odors of estrous female mice is reduced by the neurosteroid pregnenolone sulfate

Abstract

The effects of the neurosteroid, pregnenolone sulfate (PS), on the responses of male mice to the odors of estrous female mice were examined in an odor preference test. Control untreated mice displayed a significant preference for the odors of an estrous female, spending more time in a Y-maze in the vicinity of the odors of an estrous than a non-estrous female. Administration of PS decreased male preference for the odors of estrous females, causing a significant dose-related (0.01 – 10 mg/kg) decrease in the amount of time spent in the proximity of the odors of the estrous female, while having significantly less of an effect on the responses to the non-estrous female odors. Neither pregnenolone nor sodium sulfate had any significant effects on the olfactory responses. The effects of PS were significantly reduced by peripheral administrations of the non-competitive N-methyl- d-aspartate (NMDA) receptor antagonist, MK-801, but were not significantly affected by either the GABA A antagonists, bicuculline and picrotoxin, or the benzodiazepine antagonist, Ro 15–1788. These results suggest that pregnenolone sulfate has inhibitory effects on olfactory mediated male sexual interest, preference, or ‘motivation’ that, in part, involve interactions with NMDA receptor mediated mechanisms.