Effects of pulsatile infusion of the GABA(A) receptor blocker bicuculline on the onset of puberty in female rhesus monkeys

In order to test the hypothesis that GABA is an inhibitory neurotransmitter restricting the release of LHRH before puberty, we examined the effects of pulsatile infusion of the GABA(A) receptor blocker, bicuculline, on the ti ming of puberty. Eleven female monkeys at 14-15 months of age were implante d with a stainless steel cannula into the base of the third ventricle above the median eminence. Five monkeys received bicuculline infusion every 2 h at a dose of 1 mu M with a gradual increase to 100 mu M in 10 mu l using a portable infusion pump. The remaining 6 monkeys received similar infusions of saline. An additional 11 colony monkeys without cannula implantation wer e used for controls. Results indicate that bicuculline infusion advances th e timing of puberty. The age of menarche (17.8 +/- 0.5 months) in the bicuc ulline infusion animals was significantly earlier than that in the saline c ontrols (28.2 +/- 2.3, P < 0.001) as well as in colony controls (30.6 +/- 0 .9, P < 0.001). The age of first ovulation (30.5 +/- 3.3 months) in bicucul line-treated animals was much younger (P < 0.001) than that in both control s (44.8 +/- 1.8 and 44.7 +/- 1.2, respectively). Bicuculline also accelerat ed the growth curve. These results suggest that the reduction of tonic GABA inhibition of LHRH neurons advances the onset of puberty.