Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions.

Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Research Abstract Details 

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Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Abstract Text:

Christine E Marx,Lawrence J Shampine,Rahul T Khisti,William T Trost,Daniel W Bradford,A Chistina Grobin,Mark W Massing,Roger D Madison,Marian I Butterfield,Jeffrey A Lieberman,A Leslie Morrow,

Olanzapine and fluoxetine elevate the GABAergic neuroactive steroid allopregnanolone to physiologically relevant concentrations in rodent cerebral cortex. It is unknown if these agents also alter pregnenolone or deoxycorticosterone. Since olanzapine and fluoxetine in combination have clinical utility and may demonstrate synergistic effects, we investigated neuroactive steroid alterations following olanzapine, fluoxetine or coadministration. Male rats received IP vehicle, olanzapine, fluoxetine or the combination of both agents in higher-dose (0, 10, 20 or 10/20 mg/kg, respectively) and lower-dose (0, 5, 10 or 5/10 mg/kg, respectively) experiments. Pregnenolone and allopregnanolone levels in hippocampus were determined by gas chromatography/mass spectrometry. Peripheral deoxycorticosterone and other steroid levels were determined by radioimmunoassay. Olanzapine, fluoxetine or the combination increased hippocampal pregnenolone and serum deoxycorticosterone in both higher- and lower-dose experiments, and elevated hippocampal allopregnanolone in higher-dose conditions. No synergistic effects on pregnenolone or allopregnanolone were observed following olanzapine and fluoxetine coadministration compared to either compound alone. Pregnenolone and its sulfate enhance learning and memory in rodent models, and therefore pregnenolone elevations may be relevant to cognitive changes in psychotic and affective disorders. Since pregnenolone decreases have been linked to depression, it is possible that olanzapine- and fluoxetine-induced pregnenolone elevations may contribute to the antidepressant actions of these agents.

Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Publishing Authors By Initials

CE Marx,LJ Shampine,RT Khisti,WT Trost,DW Bradford,AC Grobin,MW Massing,RD Madison,MI Butterfield,JA Lieberman,AL Morrow,

For similar chemical actions and uses: pharmacologic actions: molecular mechanisms of pharmacological action: neurotransmitter agents: neurotransmitter uptake inhibitors: serotonin uptake inhibitors research abstracts see: chemical actions and uses: pharmacologic actions: molecular mechanisms of pharmacological action: neurotransmitter agents: neurotransmitter uptake inhibitors: serotonin uptake inhibitors research

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Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Pharmacology, biochemistry, and behavior

VOLUME: 84

Page Numbers: 609-17

Journal Abbreviation: Pharmacol. Biochem. Behav.

ISSN: 0091-3057

DAY: 20

MONTH: 09

YEAR: 2006

Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 367050

Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Keywords Mesh Terms:

KEYWORDS: Serotonin Uptake Inhibitors

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Information

Substance Name: Desoxycorticosterone

Registry Number: 64-85-7

Grant and Affiliation Information for Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions.

AFFILIATION: Duke University Medical Center, Durham NC, New York, NY, USA. marx0001@mc.duke.edu

Country: United States

AGENCY: United States NIMH

GRANT: K23 MH 65080

ACRONYM: MH

MEDLINETA: Pharmacol Biochem Behav

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