To determine if GABA inhibition is present in pubertal monkeys. RESULTS GABA is an inhibitory neurotransmitter restricting the onset of puberty in juvenile monkeys, and the reduction of GABA inhibition leads to the onset of puberty. Since GAD67, a rate-limiting enzyme for GABA synthesis from glutamate, is present in the monkey hypothalamus, and since in a previous study infusion of an antisense oligodeoxynucleotide (oligo) for GAD67 mRNA, which interferes with GAD synthesis, was effective in increasing LHRH release in prepubertal monkeys (J. Neurosci. 16:2563-2573, 1996), we examined the effects of the antisense oligo for GAD67 mRNA on LHRH release in pubertal rhesus monkeys (n=6, age 34.0 q 4.6 months) using push-pull perfusion. For a control, an oligodeoxynucleotide containing the same bases in a scrambled sequence was similarly examined. Direct infusion of the antisense oligo for GAD67 mRNA (1 M) into the S-ME for 6 h stimulated LHRH release LHRH release increased to 291q79% of the preinfusion levels after 4 h of infusion, reaching a peak of 406q125% at 6 h (p<0.05). Infusion of a scrambled oligo did not cause significant effects on LHRH release. The results indicate that infusion of the antisense oligo for GAD67 mRNA stimulates LHRH release in pubertal monkeys and that GABA inhibition may continue to suppress LHRH release during the pubertal period. However, since the magnitude of LHRH increase is less than half of that observed in prepubertal monkeys, GABA inhibition is weakened considerably after the onset of puberty. FUTURE DIRECTIONS This study is completed. KEY WORDS puberty, GABA, GAD67, antisense DNA RR00167
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