Lithium-induced Hypersensitivity to Foot Shock in Rats and the Role of 5-Hydroxytryptophan

Abstract

REPORTS of the behavioural effects of lithium salts on animals mainly seem to have dealt with depressant effects on spontaneous activities or with toxic symptoms (weight loss, polyuria, polydipsia, diarrhoea and so on). After prolonged lithium treatment, changes in brain 5-hydroxytryptamine (5HT) metabolism have been found to occur; 5HT turnover is decreased either in the whole brain¹ or in specific areas such as brainstem and hypothalamus^{1, 2}, where the levels are also decreased². When levels of 5HT are reduced in the whole brain of rats either by lesions³ or by parachlorophenylalanine (PCPA)⁴, an inhibitor of 5HT synthesis, motor responsiveness of rats to electrical stimulation of the feet has been found to increase. We have observed that rats treated with lithium for a few days struggle more than controls when the skin is punctured in the course of injections, and after 2 weeks of treatment with lithium chloride (LiCl), foot shock “jump response” thresholds are reduced by about 10 and 25% with doses of 1 and 2 mequiv./kg respectively. With larger doses, sensitivity to foot shock is not increased further, but may even decline as toxic effects appear; after 2 weeks of administration of 3 mequiv/kg LiCl, toxic effects appeared in nearly all our rats, and about 10% of animals died. Sheard⁵ has found that treatment for 5 days with a high dose of LiCl (5 mequiv/kg) had no effect on motor responsiveness to foot shock, although shock-induced aggressive behaviour decreased; no toxic effects were reported.