Tetanus toxin and synaptic inhibition in the substantia nigra and striatum of the rat.

1. The effects of tetanus toxin were determined on GABA-mediated synaptic inhibition of substantia nigra neurones evoked by striatal stimulation and on the presumed dopamine- and 5-hydroxytryptamine-mediated synaptic inhibition of striatal neurones evoked by nigral and dorsal raphe nucleus stimulation, respectively, in the urethane-anaesthetized rat. 2. Following an intranigral injection of tetanus toxin, striatal-evoked inhibition of substantia nigra neurones, which is sensitive to bicuculline, was rapidly abolished. This effect was not accompanied by any significant change in the responses of nigral neurones to ionophoretically administered GABA or other putative neurotransmitters and thus indicates a presynaptic site of action of the toxin. 3. The rate of onset of action of the toxin in the substantia nigra was extremely rapid (1-4 min) and appeared to be related to the rate of activation of the inhibitory pathway. 4. Injections into the substantia nigra of tetanus toxin neutralized with antitoxin had no significant effect on striatal-evoked inhibition in the substantia nigra. 5. Injections of tetanus toxin into the striatum failed to influence the inhibition of striatal neurones evoked by stimulation of the ipsilateral substantia nigra or the dorsal raphe nucleus, suggesting that tetanus toxin does not impair monoamine-mediated inhibition in the central nervous system. 6. Synaptic excitation which preceded substantia-nigra-evoked inhibition in striatal neurones and which occasionally preceded striatal-evoked inhibition in nigral neurones was also unaffected by tetanus toxin. 7. It is suggested that tetanus toxin selectively abolishes GABA-mediated synaptic inhibition in the central nervous system and may be a useful tool in the identification of such synaptic inhibitory mechanisms.