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

Publication ,  Journal Article
Marx, CE; Shampine, LJ; Khisti, RT; Trost, WT; Bradford, DW; Grobin, AC; Massing, MW; Madison, RD; Butterfield, MI; Lieberman, JA; Morrow, AL
Published in: Pharmacol Biochem Behav
August 2006

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.

Duke Scholars

Published In

Pharmacol Biochem Behav

DOI

ISSN

0091-3057

Publication Date

August 2006

Volume

84

Issue

4

Start / End Page

609 / 617

Location

United States

Related Subject Headings

  • Selective Serotonin Reuptake Inhibitors
  • Rats, Sprague-Dawley
  • Rats
  • Radioimmunoassay
  • Pregnenolone
  • Pregnanolone
  • Olanzapine
  • Neurology & Neurosurgery
  • Male
  • Hippocampus
 

Citation

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MLA
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Marx, C. E., Shampine, L. J., Khisti, R. T., Trost, W. T., Bradford, D. W., Grobin, A. C., … Morrow, A. L. (2006). Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Pharmacol Biochem Behav, 84(4), 609–617. https://doi.org/10.1016/j.pbb.2006.07.032
Marx, Christine E., Lawrence J. Shampine, Rahul T. Khisti, William T. Trost, Daniel W. Bradford, A Chistina Grobin, Mark W. Massing, et al. “Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions.Pharmacol Biochem Behav 84, no. 4 (August 2006): 609–17. https://doi.org/10.1016/j.pbb.2006.07.032.
Marx, Christine E., et al. “Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions.Pharmacol Biochem Behav, vol. 84, no. 4, Aug. 2006, pp. 609–17. Pubmed, doi:10.1016/j.pbb.2006.07.032.
Marx CE, Shampine LJ, Khisti RT, Trost WT, Bradford DW, Grobin AC, Massing MW, Madison RD, Butterfield MI, Lieberman JA, Morrow AL. Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Pharmacol Biochem Behav. 2006 Aug;84(4):609–617.
Journal cover image

Published In

Pharmacol Biochem Behav

DOI

ISSN

0091-3057

Publication Date

August 2006

Volume

84

Issue

4

Start / End Page

609 / 617

Location

United States

Related Subject Headings

  • Selective Serotonin Reuptake Inhibitors
  • Rats, Sprague-Dawley
  • Rats
  • Radioimmunoassay
  • Pregnenolone
  • Pregnanolone
  • Olanzapine
  • Neurology & Neurosurgery
  • Male
  • Hippocampus