Estrogen effects on 5-HT1A receptors in hippocampal membranes from ovariectomized rats: functional and binding studies

doi:10.1016/0006-8993(90)90983-I

Brain Research

Volume 518, Issues 1–2, 4 June 1990, Pages 287-291

https://doi.org/10.1016/0006-8993(90)90983-I Get rights and content

Abstract

Chronic treatment (4 days) of ovariectomized rats with estrogen produced a two-fold shift to left (with no change in the maximal percent inhibition) in the concentration response curve for the inhibition of adenylyl cyclase activity by 5-HT, but did not alter curves for R-PIA (adenosine A₁ agonist) or Gpp(NH)p (to activate G_i). Furthermore, estrogen treatment had no effect on the number or affinity of 5-HT_1A binding sites labeled with [³H]8-OH-DPAT. These data, when considered with the results of previous studies, suggest that estrogen treatment may selectively enhance 5-HT_1A-mediated responses in rat hippocampus.

Reference (13)

BeckS.G. et al.
Spiperone differentiates multiple 5-hydroxytryptamine responses in rat hippocampal slices in vitro
Eur. J. Pharmacol.
(1985)
BeckS.G. et al.
Chronic estrogen effects on 5-hydroxytryptamine mediated responses in hippocampal pyramidal cells of female rats
Neurosci. Lett.
(1989)
ClarkeW.P. et al.
Serotonin decreases population spike amplitude in hippocampal cells through a pertussis toxin substrate
Brain Research
(1987)
ClarkeW.P. et al.
Estrogen enhances a 5-HT_1A response in hippocampal slices from female rats
Eur. J. Pharmacol.
(1989)
YoccaF.D. et al.
BMY 7378, a buspirone analog with high affinity, selectivity and low intrinsic activity at the 5-HT_1A receptor in rat and guinea pig hippocampal membranes
Eur. J. Pharmacol.
(1987)
AndradeR. et al.
A G protein couples serotonin and GABA_B receptors to the same channels in hippocampus
Science
(1986)

There are more references available in the full text version of this article.

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: This work was supported by United States Public Health Service Grants GM-34852 and DA-01875. W.P.C. is a Revson Fellow supported by an award from the Charles H. Revson Foundation.

^b: The authors would like to thank Kelly Ann Berg and Barbara Craddock-Royal for help with the adenylyl cyclase and binding assays.

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Estrogen effects on 5-HT1A receptors in hippocampal membranes from ovariectomized rats: functional and binding studies

Abstract

Eur. J. Pharmacol.

Neurosci. Lett.

Brain Research

Eur. J. Pharmacol.

Eur. J. Pharmacol.

A G protein couples serotonin and GABAB receptors to the same channels in hippocampus

Science

Estrogen effects on 5-HT_1A receptors in hippocampal membranes from ovariectomized rats: functional and binding studies

A G protein couples serotonin and GABA_B receptors to the same channels in hippocampus