OBJECTIVE: To determine if the blockade of GABA receptors in the median eminence results in precocious puberty. RESULTS Thirteen female monkeys (14.4 q 0.3 months of age) were implanted with a stainless steel cannula into the base of the 3rd ventricle. Seven monkeys received chronic infusion of bicuculline every 2 h using a small portable infusion pump at a dose of 1 M gradually increased to 100 M. The remaining 6 monkeys served as controls. Bicuculline infusion dramatically advanced the timing of puberty. All bicuculline-treated monkeys started to exhibit an increase in sex-skin swelling by 3-5 weeks and had very early menarche. The age of menarche (18.0 q 0.4 months) in the 7 bicuculline-treated monkeys was significantly earlier than that (28.2 q 3.1) in the 6 saline controls (p< 0.001), as well as that (30.5 q 1.5, n=44) of colony controls (p<0.001). To date 3 of 7 bicuculline-treated monkeys ovulated, two died near ovulatory age, and the remaining two monkeys are still on the experimental protocol. The age of first ovulation 27.6 q 1.6 months, confirmed by elevated levels of progesterone, in 3 bicuculline-treated animals, was also much younger (p<0.01) than that in saline controls (44.7 q 1.8, n=5, one monkey has not ovulated yet) and colony controls (46.7 q 2.2, n=44). Similarly, the age of second ovulation in the 3 bicuculline-treated animals (31.5 q 1.5 months) occurred much earlier (p<0.01) than that in saline controls (45.8 q 2.2) or in colony controls (47.7 q 2.0). It is noteworthy to point out the fact that first ovulation in bicuculline-treated animals occurred even before the age of menarche in both controls. The results suggest that the reduction of tonic GABA inhibition of LHRH neurons advances the onset of puberty. FUTURE DIRECTIONS We plan to continuously observe the remaining 3 animals until ovulation. KEY WORDS puberty, GABA, bicuculline, GABAA receptors & RR00167