MALE-PREFERENCE FOR THE ODORS OF ESTROUS FEMALE MICE IS REDUCED BY THE NEUROSTEROID PREGNENOLONE SULFATE

The effects of the neurosteroid, pregnenolone sulfate (PS), on the res ponses of male mice to the odors of estrous female mice were examined in an odor preference test. Control untreated mice displayed a signifi cant 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-est rous female. Administration of PS decreased male preference for the od ors 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 odor s 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 respo nses, The effects of PS were significantly reduced by peripheral admin istrations 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 benzodiazepin e antagonist, Ro 15-1788. These results suggest that pregnenolone sulf ate has inhibitory effects on olfactory mediated male sexual interest, preference, or 'motivation' that, in part, involve interactions with NMDA receptor mediated mechanisms