The involvement of inhibitory transmitters for Ptychodiscus brevis toxin (PbTx)-induced depression of spinal synaptic transmission in neonatal rats was investigated. Stimulation of a dorsal root evoked monosynaptic reflex (MSR) and polysynaptic reflex (PSR) potentials in the segmental ventral root. The PbTx depressed the reflexes in a concentration-dependent manner and this depression was blocked by GABAA antagonist, bicuculline (1 M). GABA also produced depression of the reflexes in a concentration-dependent manner. Simultaneous application of sub maximal concentrations of PbTx (28 M) and GABA (30 M) enhanced the depression (>75%). In contrast, PbTx alone (28 M) depressed the MSR and the PSR by 33 and 47%, respectively, and GABA (30 M) alone depressed the reflexes by 30%. The N-methyl- -aspartate receptor antagonist, -2-amino-5-phosphono-pentanoic acid (10 M), blocked the PbTx-induced depression of MSR and also the enhancement of GABA response by PbTx. A glycine receptor antagonist, strychnine (1 M), failed to block the depression by the toxin up to 28 M; however, the depression was attenuated significantly at 84 M of the toxin. The results indicate that PbTx depressed the spinal reflexes via GABAA receptors. Furthermore, the potentiation of GABAergic action by PbTx requires the N-methyl-D-aspartate-dependent mechanism.