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Effects of Pulsatile Infusion of the GABA_A Receptor Blocker Bicuculline on the Onset of Puberty in Female Rhesus Monkeys¹

Wisconsin Regional Primate Research Center and Department of Pediatrics University of Wisconsin, Madison 53715-1299

Address all correspondence and requests for reprints to: Ei Terasawa, Ph.D., Wisconsin Regional Primate Research Center, 1223 Capitol Court, Madison, Wisconsin 53715-1299. E-mail: terasawa{at}primate.wisc.edu

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 timing of puberty. Eleven female monkeys at 14–15 months of age were implanted 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 µM with a gradual increase to 100 µM in 10 µl using a portable infusion pump. The remaining 6 monkeys received similar infusions of saline. An additional 11 colony monkeys without cannula implantation were used for controls. Results indicate that bicuculline infusion advances the timing of puberty. The age of menarche (17.8 ± 0.5 months) in the bicuculline infusion animals was significantly earlier than that in the saline controls (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 bicuculline-treated animals was much younger (P < 0.001) than that in both controls (44.8 ± 1.8 and 44.7 ± 1.2, respectively). Bicuculline also accelerated the growth curve. These results suggest that the reduction of tonic GABA inhibition of LHRH neurons advances the onset of puberty.

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