Orchiectomy modifies the antidepressant-like response of nicotine in the forced swimming test

Several studies have demonstrated that nicotine (NIC) exhibits antidepressant-like effects. In addition, it has been suggested that sexual hormones participate in the antidepressant actions of antidepressives. The present study was designed to analyze the effect of orchiectomy and the supplementation of testosterone propionate (TP) or 17β-estradiol (E2) on the antidepressant properties of NIC using the forced swimming test (FST), as well as to determine possible changes in the FST during different time periods after orchiectomy. In order to evaluate the influences of orchiectomy on the effects of NIC, the study first evaluated the effects of different time periods on orchiectomized rats (15, 21, 30, 45 and 60 days) that were subjected to the FST. Then, different doses of NIC (0.2, 0.4, 0.8, 1.6 mg/kg, sc) were administered for 14 days to both intact and orchiectomized rats (after 21 day) which were then also subjected to the FST. Finally, the influence of the TP or E2 supplementation on the antidepressant-like effect of NIC on orchiectomized rats (after 21 days) was also analyzed. Results reveal that orchiectomy significantly increased immobility behavior and decreased swimming and climbing up to 60 days after castration. In contrast, NIC decreased immobility behavior and increased swimming in intact rats; whereas orchiectomy suppressed this antidepressant effect of NIC. Only with E2 supplementation was it possible to restore the sensitivity of the castrated rats to NIC. These results suggest that E2 was able to facilitate the antidepressant response of NIC in orchiectomized rats.

Research Highlights
► 60 days of castration increases immobility in the forced swimming test (FST)
► Nicotine has antidepressant-like effect in the FST
► Orchiectomy blocked the antidepressive effect of nicotine in the FST
► Testosterone propionate produced no changes in the FST in orchiectomized rats
► Estrogen restores the antidepressant effect of nicotine in orchiectomized rats