Influences of the manipulation of brain catecholaminergic neuronal activity on the incidence of lidocaine-induced convulsions in mice were studied and compared with those of pentylenetetrazol (PTZ)-induced convulsions. a-Methyl-p tyrosine (a-MPT) decreased both brain noradrenaline (NA) and dopamine (DA) levels, and disulfiram decreased the NA level and increased the DA level. The inci dence of lidocaine-induced convulsions was decreased by treatments with a -MPT and disulfiram, while that of PTZ was increased by either treatment. The incidence of lidocaine-induced convulsions was slightly, but not significantly increased by L-dihy droxyphenylalanine (L-DOPA), although the brain DA level was increased by L DOPA. Methamphetamine and desipramine increased the incidences of lidocaine induced convulsions. These results may suggest that brain catecholaminergic neurons, differing from their role in inhibiting control of PTZ-seizure, act to facilitate lidocaine-induced convulsions.A major pharmacological sign of toxicity from local anesthetic administration is an ex citation of the central nervous system (CNS) as in the development of general tonic-clonic convulsions, although local anesthetics have an anticonvulsant effect in low doses (1). In travenously infused lidocaine has been shown to cause a tetraphasic action on CNS electrical activity (initially a decrease; secondarily, an increase and then decrease; and finally, an in crease in reticular neruonal firing) in cats (2). Stimulation of the CNS by local anesthetics is characterized by the activation of limbic dis charges which is most striking in the amygda loid nuclear complex (3-6) and the increase in metabolic activity which is notable in the hippocampus (7). It is generally agreed that local anesthetics induce convulsions by de pressing inhibitory neurons, thereby permit ting facilitation of excitatory neurons. This in terpretation is suggested by demonstrations that lidocaine blocked inhibitory synapses in rabbit cortical neurons, but had comparatively little effect on excitatory synapses (8), and that lidocaine facilitated the spinal monosyn aptic reflex, suggesting suppression of certain inhibitory spinal functions in preference to excitatory functions (9). y-Aminobutyric acid (GABA) is considered to be a major inhibi tory neurotransmitter in the mammalian CNS. We have demonstrated that local anesthetics inhibited GABA release from synaptosomes (10) and that intraventricularly administered

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