Olanzapine increases allopregnanolone in the rat cerebral cortex.

Published

Journal Article

BACKGROUND: The neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) has anxiolytic and anticonvulsant properties, potentiating GABA(A) receptor chloride channel function with 20-fold higher potency than benzodiazepines. Behavioral studies demonstrate that olanzapine has anxiolyticlike properties in animals, but the mechanism responsible for these effects is not clear. We examined the effect of acute olanzapine administration on cerebral cortical allopregnanolone and its relationship to serum progesterone and corticosterone levels in rats. METHODS: Male Sprague-Dawley rats were habituated to intraperitoneal (IP) saline injection for 5 days. On the day of the experiment, rats were injected with olanzapine (0, 2.5, 5.0, or 10.0 mg/kg IP, 10-11 rats per condition). Rats were sacrificed 1 hour later, and cerebral cortical allopregnanolone levels and serum progesterone and corticosterone levels were measured by radioimmunoassay. RESULTS: Olanzapine increases cerebral cortical allopregnanolone up to fourfold, depending on dose. Positive correlations were observed between cerebral cortical allopregnanolone and serum progesterone levels and between cerebral cortical allopregnanolone and serum corticosterone levels. CONCLUSIONS: Olanzapine-induced increases in the potent GABA(A) receptor modulator allopregnanolone may alter GABAergic neurotransmission, possibly contributing to antipsychotic efficacy. If allopregnanolone alterations are linked to psychotic symptom relief, neurosteroids may represent molecules for pharmacologic intervention.

Full Text

Duke Authors

Cited Authors

  • Marx, CE; Duncan, GE; Gilmore, JH; Lieberman, JA; Morrow, AL

Published Date

  • June 1, 2000

Published In

Volume / Issue

  • 47 / 11

Start / End Page

  • 1000 - 1004

PubMed ID

  • 10838068

Pubmed Central ID

  • 10838068

International Standard Serial Number (ISSN)

  • 0006-3223

Digital Object Identifier (DOI)

  • 10.1016/s0006-3223(99)00305-4

Language

  • eng

Conference Location

  • United States