Reversible effects of tetanus toxin on striatal-evoked responses and [3H]-gamma-aminobutyric acid release in the rat substantia nigra.

Abstract

1 The effects of sublethal doses of tetanus toxin on gamma-aminobutyric acid (GABA)-mediated synaptic transmission and [3H]-GABA release were studied in the rat substantia nigra. 2 Intranigral injections of tetanus toxin at 1-5 times the mouse LD50 dose produced ipsiversive circling behaviour which was maximal after 1 week and lasted 2-3 weeks. Rats then displayed normal behavior suggesting that the effects of the toxin were fully reversible. 3 In the treated nigra of circling rats there was a reduction in the striatal-evoked inhibition of compacta and reticulata neurones, but no change in their spontaneous firing rates. Some forms of striatal-evoked excitation were also reduced. Once rats had recovered from circling no alterations in the synaptic responses were detected. 4 In circling rats there were no differences in the sensitivities of neurones in the treated and untreated nigra to GABA or to other inhibitory neurotransmitters. 5 The Ca2+-dependent, K+-evoked release of [3H]-GABA from slices prepared from the treated nigra of circling rats was less than that from the untreated nigra of circling rats. No differences in nigral [3H]-GABA release were observed once rats had recovered from the circling behaviour. 6 The results demonstrate that doses of tetanus toxin which produce reversible behavioural effects can interfere reversibly with GABA-mediated synaptic transmission by a presynaptic mechanism which probably involves a reduction in transmitter release.