CHRONIC LITHIUM TREATMENT PREVENTS ATROPINE-INDUCED SUPERSENSITIVITY OF THE MUSCARINIC PHOSPHOINOSITIDE RESPONSE IN RAT HIPPOCAMPUS

Rats were placed on a lithium diet for 3 weeks or an identical diet without lithium for the same period. During the third week, atropine sulfate (10 mg/kg/day) or saline was infused via subcutaneously implanted osmotic pumps. Twenty-four hours following the removal of the pumps, brain slices and membranes were prepared from the cortex and hippocampus for determination of muscarinic stimulation of phosphoinositide turnover and for receptor-binding studies. Treatment with lithium alone did not significantly affect any of the binding or response parameters measured. Administration of atropine led to (1) an upregulation of muscarinic binding sites in both cortex and hippocampus without significant alteration in the proportion of muscarinic receptor subtypes; and (2) an enhancement of the muscarinic phosphoinositide response in hippocampal slices. However, atropine did not induce supersensitivity of the hippocampal response in rats undergoing lithium administration. These results are consistent with recent suggestions that lithium's efficacy in affective disorders may be related to a dampening of musarinic supersensitivity. © 1990.