PMID- 7914815 OWN - NLM STAT- MEDLINE DCOM- 19940921 LR - 20190614 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 645 IP - 1-2 DP - 1994 May 9 TI - Reduction of predator odor-induced anxiety in mice by the neurosteroid 3 alpha-hydroxy-4-pregnen-20-one (3 alpha HP). PG - 325-9 AB - The effects of the centrally produced allylic neurosteroid, 3 alpha-hydroxy-4-pregnen-20-one (3 alpha HP), on the responses of male mice to an aversive, anxiety-inducing, predator (cat) odor were examined in an odor preference test. Control untreated mice displayed an anxiogenic response to the cat odor, spending a minimal amount of time in a Y-maze in the vicinity of the cat odor. Intracerebroventricular (i.c.v.) administrations of 3 alpha HP had an anxiolytic action, resulting in significant dose-related (0.01-1.0 micrograms) increases in the amount of time spent in the proximity of the cat odor. These anxiolytic effects of 3 alpha HP were stereospecific, with the stereoisomer, 3 beta-hydroxy-4-pregnen-20-one (3 beta HP) having no significant effects on odor preferences. The analgesic, morphine, also had no significant effects on the response to cat odor indicating that the anxiolytic actions of 3 alpha HP were unlikely to be related to any analgesic effects. The effects of 3 alpha HP were significantly reduced by peripheral administrations of the GABAA antagonists, bicuculline and picrotoxin, but were unaffected by either the benzodiazepine antagonist, Ro 15-1788, or the opiate antagonist, naloxone. These results indicate that the allylic neurosteroid 3 alpha HP has anxiolytic actions involving interactions with the GABAA receptor. FAU - Kavaliers, M AU - Kavaliers M AD - Neuroscience Program, Faculty of Dentistry, University of Western Ontario, London, Canada. FAU - Wiebe, J P AU - Wiebe JP FAU - Galea, L A AU - Galea LA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Anti-Anxiety Agents) RN - 145-14-2 (20-alpha-Dihydroprogesterone) RN - 25680-68-6 (3-hydroxypregn-4-en-20-one) SB - IM MH - 20-alpha-Dihydroprogesterone/*analogs & derivatives/pharmacology MH - Animals MH - Anti-Anxiety Agents/pharmacology MH - Anxiety/*etiology/*psychology MH - *Cats MH - Injections, Intraventricular MH - Male MH - Mice/*physiology MH - *Odorants MH - Predatory Behavior EDAT- 1994/05/09 00:00 MHDA- 1994/05/09 00:01 CRDT- 1994/05/09 00:00 PHST- 1994/05/09 00:00 [pubmed] PHST- 1994/05/09 00:01 [medline] PHST- 1994/05/09 00:00 [entrez] AID - 0006-8993(94)91667-5 [pii] AID - 10.1016/0006-8993(94)91667-5 [doi] PST - ppublish SO - Brain Res. 1994 May 9;645(1-2):325-9. doi: 10.1016/0006-8993(94)91667-5.