ABSTRACT-Influences of drug-induced manipulations of central serotonergic function on lidocaine and pentylenetetrazol (PTZ)-induced convulsions were examined in mice. Agents that suppressed serotonergic transmission increased, whereas drugs that facilitated serotonin (5-HT) function decreased the incidence of lidocaine-induced convulsions. These treatments had similar influences on the incidence of PTZ-induced convulsions. Lidocaine (10-5-10-3 M) reduced the stimulation evoked [3H]5-HT release from cortical slices, followed with an increased spontaneous [3H] overflow at higher concentrations. These results may suggest that brain 5-HT neurons are causally involved as inhibitory neurons in lidocaine-induced convul sions as in the case of PTZ-induced convulsions.Keywords: Lidocaine, Convulsion, Serotonin Intravenously infused local anesthetics have been shown to cause polyphasic actions on central nervous system (CNS) electrical activity (initially decrease, then increase and decrease and finally increase reticular neuro nal firing) in cats (1). Stimulation of the CNS by local anesthetics is characterized by the activation of limbic dis charges, which is most striking in the amygdaloid nuclear complex, and the increase in metabolic activity, notable in the hippocampus (2, 3). A major pharmacological sign of toxicity from local anesthetic administration is an exci tation of the CNS as in the development of general tonic clonic convulsions. It is generally agreed that local anesthetics induced convulsions by depressing inhibitory neurons, thereby permitting facilitation of excitatory neu rons, although the precise mechanism of convulsion in duction still remaines unsolved.We have suggested that the inhibition of the function of r-aminobutyric acid (GABA) by local anesthetics through inhibiting GABA release from the neurons may be a major cause underlying the mechanisms of the induc tion of the convulsions (4). It is also suggested that brain monoamines such as norepinephrine, dopamine and serotonin (5-HT) serve as inhibitory neurotransmitters in several experimental models for convulsions. However, the stimulatory influence of brain catecholaminergic and serotonergic neurons on lidocaine-induced convulsions have been reported (5, 6). Therefore, aminergic influences on local anesthetic-induced convulsions seem different from other drug-induced convulsion models. However, the causal relationship between brain 5-HT neurons and local anesthetic-induced convulsions is yet unclear.The present study investigated the role of brain 5-HT neurons in local anesthetic-induced convulsions in com parison with that in PTZ-induced convulsions.Male dd-strain mice weighing from 20 to 25 g were used. The injections of convulsants were performed be tween 2:00 PM and 5:00 PM because of the effects of cir cadian rhythms on these experiments. Animals had free access to food and water until 3 hr before the experi ments. p-Chlorophenylalanine (PCPA) was suspended in 0.3076 carboxymethylcellulose solution. Other drugs were dissolved in saline....

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