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Region-specific regulation of 5-HT1B receptors in the rat brain by chronic venlafaxine treatment.

Psychopharmacology (Berl.). 2013 Sep;229(1):177-85. doi:10.1007/s00213-013-3104-y. Epub 2013 Apr 23
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摘要


RATIONALE:Venlafaxine is a non-selective serotonin and noradrenaline reuptake inhibitor antidepressant drug for which clinical studies have suggested a high level efficacy and a possible early action onset compared to the classical antidepressants. Its therapeutic effects might be due, at least in part, to adaptive changes in serotonergic neurotransmission, through the activation of the different 5-HT receptor subtypes. 5-HT(1B) receptors are located in the axon terminals of both serotonergic and non-serotonergic neurons, where they act as inhibitory autoreceptors or heteroreceptors, respectively. However, the information about the involvement of this subtype in the mechanism of action of antidepressants is limited and quite controversial. OBJECTIVES:The aim of this study was to evaluate the effect of venlafaxine (10 mg kg⁻¹ day⁻¹, p.o.) after 21 days of treatment on the density of 5-HT(1B) receptors and their functionality in rat brain. METHODS:Effects of chronic venlafaxine were evaluated at different levels of 5-HT(1B) receptor by using receptor autoradiography, [³⁵S]GTPγS binding, and the regulation of body temperature induced by selective 5-HT(1B) agonist. RESULTS:Our results show that venlafaxine induced an increase in sensitivity of 5-HT(1B) receptors in hypothalamus both at G-protein level and the control of core temperature without affecting the receptor density. CONCLUSIONS:These results demonstrate that adaptive changes on 5-HT(1B) receptors induced by chronic administration of venlafaxine exhibit regional differences suggesting that the hypothalamus might be an important site of drug action.

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