Inhibition of proestrous LH surge and ovulation in rats evoked by stimulation of the medial raphe nucleus involves a GABA-mediated mechanism.

The neurotransmitters involved in the inhibition of luteinizing hormone (LH) release induced by electrochemical stimulation (anodic d.c., 100 microA/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 gamma-aminobutyric acid (GABA) antagonists, picrotoxin (0.8 mg/kg, i.p.) and bicuculline (6 mg/kg, i.p.). Injection of 5-HT (15 micrograms) 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 micrograms) 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.