Agomelatine is an antidepressant with a novel mechanism of action. It is a melatonergic agonist for MT1 and MT2 receptors and a serotonin (5-HT)2C receptor antagonist. Unlike selective serotonin reuptake inhibitors (SSRIs), agomelatine has been suggested not to have sexual dysfunction. Melatonin is suggested to have effects on hypothalamic-pituitary-gonadal (HPG) axis. Our previous study showed that melatonin directly affected GT1-7 cells, immortalized GnRH neurons, increasing intracellular free calcium levels ([Ca2+]i). However, the effects of agomelatine on reproductive functions have not been sufficiently studied in animal models. Therefore, in this study, we aimed to explore the effects of agomelatine in male and female rats. For the experimental studies, male and female Sprague Dawley rats were used. Each group consisted of 10 rats. The animals started to receive daily oral agomelatine (10 mg/kg) on post-natal day 21. The control group received only vehicle. Puberty onset was monitored by examination of vaginal opening and preputial separation in female and male rats, respectively. Changes of body weight and food intake were daily monitored. The female rats were decapitated under general anesthesia with xylazine (80 mg/kg)/ketamine (12 mg/kg) cocktail on the first diestrus following 90 days. The male rats were maintained until 120 days for analyzing sexual behaviour and antidepressant efficiacy, which was assessed using the forced swimming test (FST). Agomelatine advanced vaginal opening in the female rats (48.9±1.1 days vs 43.1±0.7 days for control rats, p<0.001) whereas it delayed puberty onset in male rats (45.8±0.5 days vs. 50.2±0.9 days for control rats, p<0.001). Pubertal weight was significantly higher in agomelatine-treated male rats (165.5±3.74 g vs 144.29±3.53 g for control rats, p<0.001) whereas there was no any significant change in female rats. None of the parameters related to sexual behaviour showed significant differences between agomelatine-treated and control male rats except intromission frequency (IF). Agomelatine decreased IF (18.9±1.5 vs 26.5±2.3 for control rats, p<0.05), which indicates a facilitator role of this antidepressant on male sexual behaviour. Agomelatine was very active in the FST at 10mg/kg and induced a significant decrease (p<0.01) in duration of immobility (67.3±4.9 vs. 103.7±9.5 for control rats). The swimming time was significantly increased by agomelatine (145.7±7.8 vs. 113.7±5.4 for control rats, p<0.01). The present findings suggest that agomelatine shows a strong antidepressant effect in male rats without any adverse influences on sexual behaviour, and its effects on pubertal maturation seem to show sex-dependent differences.
Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC090
Poster Communications: Sex dependent effects of agomelatine on reproductive functions in rats
H. Kelestimur1, N. Ulker1, A. Yardimci1, O. Bulmus1, S. Canpolat1, M. Ozcan2
1. Department of Physiology, Firat University Medical School, Elazig, Turkey. 2. Department of Biophysics, Firat University Medical School, Elazig, Turkey.
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Where applicable, experiments conform with Society ethical requirements.