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Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats.

ABSTRACT: The 5-HT(4) receptor may be a target for antidepressant drugs. Here we have examined the effects of the dual antidepressant, venlafaxine, on 5-HT(4) receptor-mediated signalling events.The effects of 21 days treatment (p.o.) with high (40?mg·kg(-1)) and low (10?mg·kg(-1)) doses of venlafaxine, were evaluated at different levels of 5-HT(4) receptor-mediated neurotransmission by using in situ hybridization, receptor autoradiography, adenylate cyclase assays and electrophysiological recordings in rat brain. The selective noradrenaline reuptake inhibitor, reboxetine (10?mg·kg(-1), 21 days) was also evaluated on 5-HT(4) receptor density.Treatment with a high dose (40?mg·kg(-1)) of venlafaxine did not alter 5-HT(4) mRNA expression, but decreased the density of 5-HT(4) receptors in caudate-putamen (% reduction = 26 ± 6), hippocampus (% reduction = 39 ± 7 and 39 ± 8 for CA1 and CA3 respectively) and substantia nigra (% reduction = 49 ± 5). Zacopride-stimulated adenylate cyclase activation was unaltered following low-dose treatment (10?mg·kg(-1)) while it was attenuated in rats treated with 40?mg·kg(-1) of venlafaxine (% reduction = 51 ± 2). Furthermore, the amplitude of population spike in pyramidal cells of CA1 of hippocampus induced by zacopride was significantly attenuated in rats receiving either dose of venlafaxine. Chronic reboxetine did not modify 5-HT(4) receptor density.Our data indicate a functional desensitization of 5-HT(4) receptors after chronic venlafaxine, similar to that observed after treatment with the classical selective inhibitors of 5-HT reuptake.

SUBMITTER: Vidal R

PROVIDER: S-EPMC2990165 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats.

Vidal R R Valdizan E M EM Vilaró M T MT Pazos A A Castro E E

British journal of pharmacology 20101001 3

<h4>Background and purpose</h4>The 5-HT(4) receptor may be a target for antidepressant drugs. Here we have examined the effects of the dual antidepressant, venlafaxine, on 5-HT(4) receptor-mediated signalling events.<h4>Experimental approach</h4>The effects of 21 days treatment (p.o.) with high (40 mg·kg(-1)) and low (10 mg·kg(-1)) doses of venlafaxine, were evaluated at different levels of 5-HT(4) receptor-mediated neurotransmission by using in situ hybridization, receptor autoradiography, aden ...[more]

PMID: 20880406

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Dataset Information

Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats.

Publications

Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats.

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