Chronic fluoxetine induces opposite changes in G protein coupling at pre and postsynaptic 5-HT 1A receptors in rat brain

Chronic fluoxetine induces opposite changes in G protein coupling at pre and postsynaptic 5-HT 1A... Chronic treatment with the antidepressant fluoxetine may lead to changes in the properties of pre- and postsynaptic 5-HT 1A receptors due to modifications in the receptor-G protein coupling process. We have evaluated, in rats, the effect of chronic fluoxetine (10 mg/kg/day) at brain 5-HT 1A receptors using different techniques. The density of 5-HT 1A receptors was unchanged in fluoxetine-treated rats vs. vehicle group. Stimulation of ( 35 S)GTPγS binding induced by (±)8-OH-DPAT was significantly attenuated in dorsal raphe nucleus after fluoxetine (+3.7 vs. +31.2% in vehicle). The inhibition of dorsal raphe firing by (±)8-OH-DPAT (ED 50 in vehicle = 2.1 μg/kg, i.v.) was also attenuated in rats treated with fluoxetine (ED 50 =4.7 μg/kg). In contrast, a significant increase on (±)8-OH-DPAT-induced stimulation of ( 35 S)GTPγS binding was observed in CA 1 (+53.4 vs.+20.2% in vehicle) and dentate gyrus (+105.7 vs. +52.6% in vehicle) but not in entorhinal cortex. Our data demonstrate that fluoxetine-induced desensitization of 5-HT 1A autoreceptors occurs at G protein level. Moreover, a relevant finding is the region-specific hypersensitivity of postsynaptic 5-HT 1A receptors, in the hippocampus but not in entorhinal cortex, following chronic fluoxetine. These differential adaptive changes in brain 5-HT 1A receptors could underlie the mechanism of action of antidepressants and also contribute to their clinical effects. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Chronic fluoxetine induces opposite changes in G protein coupling at pre and postsynaptic 5-HT 1A receptors in rat brain

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Publisher
Elsevier
Copyright
Copyright © 2002 Elsevier Science Ltd
ISSN
0028-3908
eISSN
1873-7064
DOI
10.1016/S0028-3908(02)00340-4
Publisher site
See Article on Publisher Site

Abstract

Chronic treatment with the antidepressant fluoxetine may lead to changes in the properties of pre- and postsynaptic 5-HT 1A receptors due to modifications in the receptor-G protein coupling process. We have evaluated, in rats, the effect of chronic fluoxetine (10 mg/kg/day) at brain 5-HT 1A receptors using different techniques. The density of 5-HT 1A receptors was unchanged in fluoxetine-treated rats vs. vehicle group. Stimulation of ( 35 S)GTPγS binding induced by (±)8-OH-DPAT was significantly attenuated in dorsal raphe nucleus after fluoxetine (+3.7 vs. +31.2% in vehicle). The inhibition of dorsal raphe firing by (±)8-OH-DPAT (ED 50 in vehicle = 2.1 μg/kg, i.v.) was also attenuated in rats treated with fluoxetine (ED 50 =4.7 μg/kg). In contrast, a significant increase on (±)8-OH-DPAT-induced stimulation of ( 35 S)GTPγS binding was observed in CA 1 (+53.4 vs.+20.2% in vehicle) and dentate gyrus (+105.7 vs. +52.6% in vehicle) but not in entorhinal cortex. Our data demonstrate that fluoxetine-induced desensitization of 5-HT 1A autoreceptors occurs at G protein level. Moreover, a relevant finding is the region-specific hypersensitivity of postsynaptic 5-HT 1A receptors, in the hippocampus but not in entorhinal cortex, following chronic fluoxetine. These differential adaptive changes in brain 5-HT 1A receptors could underlie the mechanism of action of antidepressants and also contribute to their clinical effects.

Journal

NeuropharmacologyElsevier

Published: Jan 1, 2003

References

  • A review of central 5-HT receptors and their function
    Barnes, N.M.; Sharp, T.
  • Region-specific changes in 5-HT 1A receptor-activated G-proteins in rat brain following chronic buspirone
    Sim-Selley, L.J.; Vogt, L.J.; Xiao, R.; Childers, S.R.; Selley, D.E.

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