To ascertain whether endogenous gamma-aminobutyric acid (GABA) exists and exerts physiological effects in the optic nerve, we compared the effects of GABA and related drugs on the neonatal (1 to 22 days of age) and adult (greater than 6 months) rat optic nerve in vitro. GABA (10(-4)-10(-3) M) reversibly depressed the amplitude and increased the latency of compound action potentials in the neonatal optic nerve. In the adult optic nerve, GABA (10(-4)-10(-3) M) had no significant effect on the compound action potential. The GABA-A receptor agonist, isoguvacine (10(-4)-10(-3) M), mimicked these GABA effects on the neonate and adult optic nerve. Lower concentrations (10(-5) M) of GABA increased excitability of the neonatal optic nerve but produced no discernible effects on the adult optic nerve. The GABA-uptake inhibitor, nipecotic acid (10(-3) M), mimicked the effects of GABA (10(-5) M) on the neonatal optic nerve. The GABA-A receptor blockers, picrotoxin and bicuculline (10(-6)-10(-3) M), decreased the latency of compound action potentials in the neonatal optic nerve. Membrane potential recordings indicate that while GABA (10(-5)-10(-3) M) depolarized the neonatal optic nerve dose-dependently, picrotoxin hyperpolarized the axons. In the adult optic nerve, neither GABA-uptake inhibitors nor GABA-A receptor blockers had significant effects on the compound action potential. These results suggest that functional GABA-A receptors and GABA are present in the neonatal rat optic nerve and depolarize axons under physiological conditions. However, this does not appear to be the case in the adult optic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)