Vilazodone does not inhibit sexual behavior in male rats in contrast to paroxetine: A role for 5-HT1A receptors?
نویسندگان
چکیده
Vilazodone (VLZ) is a selective serotonin reuptake inhibitor (SSRI) and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder in adults. In preclinical studies, VLZ had significantly lower sexual side effects than SSRIs and reduced serotonin transporter (SERT) levels in forebrain regions. In the current study, once-daily paroxetine (PAR, 10 mg/kg), VLZ (10 mg/kg), PAR + buspirone (BUS, 3 mg/kg; a 5-HT1A partial agonist), or vehicle (VEH) was administered to male rats for 2 weeks then switched for 7 days (eg, PAR switched to VLZ, PAR + BUS, or VEH). Sexual behavior (eg, ejaculation frequency and latency) was evaluated 1-hr postdose on days 1, 7, 14, and 21. After 2 weeks, treatment with PAR but not VLZ resulted in a significant decrease in sexual behavior. In a 30-min test, the range of ejaculation frequency was 3.08-3.5 with VLZ and 1.00-1.92 with PAR (P < 0.05 vs VEH). After switching from PAR to VEH, PAR + BUS, or VEH, sexual behaviors were normalized to control levels. In contrast, the switch from VLZ to PAR resulted in reduced sexual behaviors. This preclinical study showed that unlike PAR, an SSRI with no 5-HT1A receptor activity, initial treatment with VLZ did not result in sexual side effects at therapeutically relevant doses. Results in male rats switched from PAR to VLZ or PAR + BUS strongly suggest that activation of 5-HT1A receptors may mitigate the sexual side effects associated with conventional SSRIs.
منابع مشابه
Role of 5-Hydroxytryptamine 1A Receptors in 6-Hydroxydopmaine-induced Catalepsy-like Immobilization in Rats: a Therapeutic Approach for Treating Catalepsy of Parkinson’s Disease
We have shown that buspirone, a partial agonist of 5-hydroxytryptamine 1A (5-HT1A) receptors, improves motor dysfunctions induced by 6-hydroxydopamine (6-OHDA) and haloperidol in rats. The present work extends these findings by investigating the role of 5-HT1A receptors on catalepsy-like immobilization in rats, a model of Parkinson’s disease. Catalepsy was induced by unilateral infusion of 6-OH...
متن کاملRole of 5-Hydroxytryptamine 1A Receptors in 6-Hydroxydopmaine-induced Catalepsy-like Immobilization in Rats: a Therapeutic Approach for Treating Catalepsy of Parkinson’s Disease
We have shown that buspirone, a partial agonist of 5-hydroxytryptamine 1A (5-HT1A) receptors, improves motor dysfunctions induced by 6-hydroxydopamine (6-OHDA) and haloperidol in rats. The present work extends these findings by investigating the role of 5-HT1A receptors on catalepsy-like immobilization in rats, a model of Parkinson’s disease. Catalepsy was induced by unilateral infusion of 6-OH...
متن کاملEffects of vilazodone on sexual functioning in healthy adults: results from a randomized, double-blind, placebo-controlled, and active-controlled study
The aim of this study is to evaluate the effects of vilazodone on sexual functioning in healthy, sexually active adults and assess the impact of medication nonadherence in this type of trial. Participants were randomized to vilazodone (20 or 40 mg/day), paroxetine (20 mg/day), or placebo for 5 weeks of double-blind treatment. The primary endpoint was change from baseline to day 35 in Change in ...
متن کاملEffects of chronic paroxetine pretreatment on (+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin induced c-fos expression following sexual behavior.
Chronic treatment with the selective serotonin reuptake inhibitor paroxetine impairs the functioning of 5-HT(1A) receptors involved in ejaculation. This could underlie the development of delayed ejaculation often reported by men treated with paroxetine. The neurobiological substrate linking the effects of selective serotonin reuptake inhibitor-treatment and 5-HT(1A) receptor activation with eja...
متن کاملP2: The Role of Neuronal Nitric Oxide Synthase on the Anti-Seizure Effects of 5-HT1A Receptors in Perforant Pathway Kindling Model in Rat
Neuronal nitric oxide synthase (nNOS) plays a role in synaptic potentiation and kindling process.The relationship between nNOS and 5-HT1A receptors also nearly has been specified. In this research,we investigate the role of nNOS on the anticonvulsant effect of 5-HT1A receptors. 24 male (280 ± 30 g) were randomly assigned to four groups (vehicle,NI,Way 100635 and NI + Way100635) (n = 6). ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Neuropharmacology
دوره 107 شماره
صفحات -
تاریخ انتشار 2016