Estrogen desensitizes 5-HT 1A receptors and reduces levels of G z , G i1 and G i3 proteins in the hypothalamus

Estrogen desensitizes 5-HT 1A receptors and reduces levels of G z , G i1 and G i3 proteins in the... The present study investigated whether estrogen would desensitize hypothalamic serotonin 1A (5-HT 1A ) receptors by examining the neuroendocrine response to 8-OH-DPAT, a 5-HT 1A agonist. Rats were ovariectomized, allowed to recover for 5 days, then given 2 daily injections of estradiol benzoate or vehicle (10 μg/day, s.c.). Twenty-four hours after the second injection, rats were challenged with a sub-maximal dose of 8-OH-DPAT (50 μg/kg, sc) or saline 15 min prior to sacrifice. 8-OH-DPAT produced a significant increase in plasma oxytocin, ACTH and corticosterone levels in ovariectomized rats. While estrogen treatment for 2 days did not alter basal hormone levels, it did significantly reduce the magnitude of oxytocin, ACTH and corticosterone responses to 8-OH-DPAT. The reduction in hormone responses was accompanied by a significant reduction in hypothalamic levels of G z , G i1 and G i3 proteins (by 50%, 30% and 50%, respectively). These findings suggest that a reduction in these G proteins may contribute to the mechanisms underlying estrogen-induced desensitization of 5-HT 1A receptors. The desensitization of 5-HT 1A receptors has been suggested to underlie the therapeutic effects of antidepressant 5-HT uptake inhibitors (SSRIs). Thus, the present results suggest that estrogen or estrogen-like substances in combination with SSRIs may prove effective in developing novel therapeutic strategies for neuropsychiatric disorders in women. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Estrogen desensitizes 5-HT 1A receptors and reduces levels of G z , G i1 and G i3 proteins in the hypothalamus

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Publisher
Elsevier
Copyright
Copyright © 2000 Elsevier Science Ltd
ISSN
0028-3908
eISSN
1873-7064
DOI
10.1016/S0028-3908(99)00264-6
Publisher site
See Article on Publisher Site

Abstract

The present study investigated whether estrogen would desensitize hypothalamic serotonin 1A (5-HT 1A ) receptors by examining the neuroendocrine response to 8-OH-DPAT, a 5-HT 1A agonist. Rats were ovariectomized, allowed to recover for 5 days, then given 2 daily injections of estradiol benzoate or vehicle (10 μg/day, s.c.). Twenty-four hours after the second injection, rats were challenged with a sub-maximal dose of 8-OH-DPAT (50 μg/kg, sc) or saline 15 min prior to sacrifice. 8-OH-DPAT produced a significant increase in plasma oxytocin, ACTH and corticosterone levels in ovariectomized rats. While estrogen treatment for 2 days did not alter basal hormone levels, it did significantly reduce the magnitude of oxytocin, ACTH and corticosterone responses to 8-OH-DPAT. The reduction in hormone responses was accompanied by a significant reduction in hypothalamic levels of G z , G i1 and G i3 proteins (by 50%, 30% and 50%, respectively). These findings suggest that a reduction in these G proteins may contribute to the mechanisms underlying estrogen-induced desensitization of 5-HT 1A receptors. The desensitization of 5-HT 1A receptors has been suggested to underlie the therapeutic effects of antidepressant 5-HT uptake inhibitors (SSRIs). Thus, the present results suggest that estrogen or estrogen-like substances in combination with SSRIs may prove effective in developing novel therapeutic strategies for neuropsychiatric disorders in women.

Journal

NeuropharmacologyElsevier

Published: Sep 1, 2000

References

  • Diagnostic dilemmas presented by patients with anxiety and depression
    Goldberg, R.J.
  • 5-HT inhibits lateral entorhinal cortical neurons of the rat in vitro by activation of potassium channel-coupled 5-HT 1A receptors
    Grünschlag, C.R.; Haas, H.L.; Stevens, D.R.
  • Prior treatment with estrogen attenuates the effects of the 5-HT 1A agonist, 8-OH-DPAT, on lordosis behavior
    Jackson, A.; Uphouse, L.
  • Dose-dependent effects of estradiol benzoate on 5-HT 1A receptor agonist action
    Jackson, A.; Uphouse, L.
  • Characterization of the K + current mediated by 5-HT 1A receptor in the acutely dissociated rat dorsal raphe neurons
    Katayama, J.; Yakushiji, T.; Akaike, N.
  • Long-term fluoxetine treatment decreases 5-HT 1A receptor responsivity in obsessive-compulsive disorder
    Lesch, K.P.; Schulte, H.M.; Osterheider, M.; Muller, T.
  • Autoradiographic evidence for differential G-protein coupling of 5-HT 1A receptors in the rat brain: lack of effect by repeated injections of fluoxetine
    Li, Q.; Battaglia, G.; Van de Kar, L.D.
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    Rhee, J.S.; Ishibashi, H.; Akaike, N.
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    Ulrich, U.; Nowara, I.; Rossmanith, W.G.
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    Van de Kar, L.D.; Levy, A.D.; Li, Q.; Brownfield, M.S.
  • WAY-100635 inhibits 8-OH-DPAT stimulated oxytocin, ACTH, and corticosterone, but not prolactin secretion
    Vicentic, A.; Li, Q.; Battaglia, G.; Van de Kar, L.D.

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