Influence of castration on the response of the rat vas deferens to fluoxetine

Antidepressant drugs such as desipramine and fluoxetine increase norepineph rine (NE) contractile response in rat vas deferens by inhibiting neuronal a mine uptake. Fluoxetine, unlike other antidepressants, also inhibits calciu m fluxes, which results in an inhibition of maximal NE effect.. Since the c ontractile response of the reproductive tract is under the influence of tes tosterone, the effect of fluoxetine could be modified according to the endo crine status of the animal. In the present study we evaluated the influence of castration and testosterone replacement (1 mg per 100 g body wt.) on th e peripheral action of fluoxetine. Castration was followed by a decrease in vas deferens weight and the appearance of spontaneous activity. Testostero ne replacement reversed these effects. Concentration-response curves to NE and calcium were obtained in the absence and the presence of fluoxetine in vasa deferentia from normal, castrated and testosterone-treated castrated r ats. After castration the effect of fluoxetine on vas deferens contractilit y was markedly altered. The spontaneous activity that appears after castrat ion was prevented by fluoxetine and the stimulatory effect on NE-induced co ntractions was not observed. In contrast, the inhibitory action of fluoxeti ne on maximal NE effect was increased. Testosterone replacement restored va s deferens response to NE in the presence of fluoxetine. Fluoxetine did not modify the binding parameters of [H-3]prazosin in vasa deferentia from nor mal or castrated animals. Cocaine shifted the NE concentration-response cur ve to the left in all groups, suggesting that the changes in fluoxetine eff ect following castration were not the result of an alteration of the neuron al uptake mechanism. The nitric oxide synthase inhibitor L-NMMA did not mod ify vas deferens response to NE in castrated animals either in the absence or presence of fluoxetine. An increased sensitivity to the inhibitory effec t of fluoxetine was observed in the calcium concentration-response curves i n vasa deferentia from castrated rats, an effect that was reversed by testo sterone replacement. The results suggest that the alteration in the respons iveness of vasa deferentia from castrated rats to calcium could be responsi ble for increased sensitivity to the inhibitory effect of fluoxetine. It is concluded that vas deferens contractile response is testosterone dependent and that this behaviour modifies the effect of drugs such as fluoxetine th at have dual effect on contractility. (C) 2000 Academic Press.