alpha-MSH is involved in reproductive processes and can regulate the expression of lordosis, an important component of female reproductive behavior in rats and many other species. In this study, we investigated the effects of MSH peptides on lordosis behavior when injected in medial preoptic area (POA) of ovariectomised rats primed with estradiol. The results show an increase in lordotic activity after bilateral administration of alpha-MSH and gamma-MSH. Interestingly, the treatment with the MC4 receptor antagonist HS014 did not block the stimulatory effect of alpha-MSH. Moreover, the injection of HS014 did not itself modify the lordosis quotient. Nitric oxide has been suggested to play a crucial role in the regulation of lordosis behavior via stimulation of guanylyl cyclase to synthesize cGMP. In order to determine the participation of NO in the effect of the melanocortins, another group of rats were treated with L-NAME, an inhibitor of NOS, alone or 15 min before the injection of alpha-MSH or gamma-MSH. The injection of L-NAME into the POA of E-primed rats 15 min before the test for sexual receptivity did not modify significantly the lordosis quotient at the two doses examined. The treatment with L-NAME at the lowest dose completely abolished the stimulatory effect of alpha-MSH and gamma-MSH on sexual behavior. The results indicate that the effects of MSH peptides on female sexual behavior in this area are mediated through specific MC receptor, that could be the MC3 receptor and that NO mediates the melanocortins effects.