Lithium is one of the most effective drugs available for the treatment of psychiatric disorders, as it is therapeutic in approximately 80% of manic-depressive patients and it reduces the manifestations of both phases of the illness. Thus, the intriguing conjugation of the simplest drug known to man effectively treating disorders of great complexity, those involving emotion and behavior. Lithium is a mood-stabilizer; it seems to support homeostatic mechanisms that strive to maintain a balance in the responses to stimuli, which cause fluctuations in mood. Thus, learning the mechanism of action of lithium may increase the understanding of the neurochemical basis of emotion and of related disorders. This chapter describes experimental results, which show that lithium selectively increases cholinergic activity in mammalian brain in vivo. Furthermore, at appropriate doses, the co-administration of lithium and cholinomimetics results in seizures, which are generalized to all regions of the brain that have been examined, and which are difficult to control pharmacologically, leading invariably to death. A tremendously large increase in the concentrations of acetylcholine and choline accompany the seizures, as do increases in the products of the phosphoinositide second messenger system. Potential mechanisms that might mediate the stimulatory effects of lithium on cholinergic function are discussed.
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