Reversible effects of tetanus toxin on striatal-evoked responses and [3H]-gamma-aminobutyric acid release in the rat substantia nigra.
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.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D005260:Female; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D013744:Tetanus Toxin / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D013744:Tetanus Toxin; D005680:gamma-Aminobutyric Acid