[Effect of long-term lithium treatment on serotonin syndrome in rats]

Brain 5-HT receptors are reported to play an important role in the therapeutic effect of Li in manic-depressive illness. In the present study we examined the effect of Li on 5-HT syndrome which is postulated to be the physiological response of 5-HT1 receptors. Intraperitoneal injection of the 5-HT receptor agonist 5-MeODMT elicited 5-HT syndrome in a dose-dependent manner. Then the incidence of 5-HT syndrome elicited by 2 mg/kg of 5-MeODMT was measured in animals under long-term Li treatment. Four out of six abnormal behaviors of the 5-HT syndrome, i.e. forepaw treading, resting tremor, rigidity, and head weaving, were significantly increased by the 9-day treatment with Li. On the 17th day of Li treatment, the incidence of all six behaviors, including hindlimb abduction and straub tail, were significantly enhanced. This Li-induced supersensitivity of 5-HT1 receptor-mediated behaviors inconsistent with the previous reports of the down-regulation of 5-HT1 receptors measured by receptor binding assay. The reason for this discrepancy is obscure. Further examination of the effect of Li on the signal-transduction system from the receptor to the behavior will be necessary.