Sexual side effects of serotonergic antidepressants: Mediated by inhibition of serotonin on central dopamine release?

被引：59
作者：
Bijlsma, Elisabeth Y. [1 ,2 ]
Chan, Johnny S. W. [1 ,2 ]
Olivier, Berend [1 ,2 ]
Veening, Jan G. [1 ,2 ]
Millan, Mark J. [3 ,4 ]
Waldinger, Marcel D. [1 ,2 ]
Oosting, Ronald S. [1 ,2 ]
机构：
[1] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CG Utrecht, Netherlands
[2] Univ Utrecht, Rudolf Magnus Inst Neurosci, NL-3584 CG Utrecht, Netherlands
[3] Inst Rech Servier, Dept Psychopharmacol, F-78290 Croissy Sur Seine, France
[4] Radboud Univ Nijmegen, Med Ctr, Dept Anat, NL-6525 ED Nijmegen, Netherlands
来源：
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR | 2014年 / 121卷
关键词：
Antidepressants; Animal model; Sexual dysfunction; Sexual behavior; Ejaculation; Drug-induced; RAT EJACULATORY BEHAVIOR; NUCLEUS-ACCUMBENS DOPAMINE; LATERAL HYPOTHALAMIC AREA; SELECTIVE SEROTONIN; REUPTAKE INHIBITOR; DOUBLE-BLIND; PREMATURE EJACULATION; PREOPTIC AREA; COPULATORY-BEHAVIOR; DEPRESSED-PATIENTS;
D O I：
10.1016/j.pbb.2013.10.004
中图分类号：
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号：
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要：
Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone. DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. (C) 2013 Elsevier Inc. All rights reserved.
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收藏
页码：88 / 101
页数：14
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