The neurotransmitters involved in the inhibition of luteinizing hormone (LH) release induced by electrochemical stimulation (anodic d.c, 100 µA/30 s) of the medial raphe nucleus (MRn) were studied. Stimulation applied at noon on the day of proestrus blocked the preovulatory surge of LH and ovulation. This effect was prevented by pretreating the animals (15 min before stimulation) with the 5-HT antagonist, methysergide (3.5 mg/kg, i.p.) The inhibition of LH release induced by stimulation of the MRn was also suppressed by the injection of the γ-aminobutyric acid (GABA) antagonists, picrotoxin (0.8 mg/kg, i.p.) and bicuculline (6 mg/kg, i.p.). Injection of 5-HT(15 µg) into the third ventricle on the day of proestrus mimicked the effect of MRn stimulation, a response which was prevented by methysergide, picrotoxin or bicuculline. An intraventricular injection of GABA (10 µg) also inhibited the preovulatory surge of LH and ovulation, but whereas the administration of bicuculline prevented the effect of GABA, that of methysergide failed to produce any change. It is concluded that stimulation of the MRn inhibits the proestrous surge of LH by activating a serotonergic pathway and that the effect is mediated by GABAergic neurons.

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The effect of the serotonergic system on glutamic acid decarboxylase (GAD) activity of the preoptic area and the hypothalamus was studied in female rats on the day of proestrus. A circadian rhythm of GAD activity was observed with higher values in rats killed at 1130 h than in rats killed at 1500 h. In rats bearing lesions of the median raphe nucleus (MRn), a nucleus that sends 5-hydroxytryptamine nerve terminals to the areas under study decreased GAD activity. On the contrary, electrochemical stimulation of the MRn enhanced GAD activity in intact rats killed at 1500 h, but not in those killed at 1130 h, an effect that was prevented by the injection of the 5-hydroxytryptamine antagonist, methysergide. Furthermore, the injection of 5-hydroxytryptamine into the third ventricle, either in intact rats in the afternoon or in MRn-lesioned rats in the morning, also increased GAD activity. The results of the present study suggest that activation of the serotonergic system increases GAD activity in the preoptic area and hypothalamus.