Effect of Chronic Lithium Treatment on 5‐Hydroxytryptamine Autoreceptors and Release of 5‐[3H]Hydroxytryptamine from Rat Brain Cortical, Hippocampal, and Hypothalamic Slices

Abstract

The effect of acute and chronic lithium treatments on 5-hydroxytryptamine (5-HT, serotonin) release and on its regulation by presynaptic 5-HT autoreceptors was studied in [³H]5-HT preloaded superfused rat brain slices. The [³H]5-HT overflow evoked by a 30-s exposure to 65 mM K⁺ was increased after 3 weeks of ingestion of lithium-containing diet in the three brain areas examined. Acute injection of 4 mEq/kg lithium chloride did not affect 5-HT release. The K⁺-induced release observed in both control and chronically lithium-treated animals was Ca²⁺-dependent. Chronic lithium treatment was also found to be associated with a decrease in basal [³H]5-HT overflow in the cortex and hypothalamus and with an increase in spontaneous hippocampal 5-HT overflow. The Ca²⁺-independent overflow induced by fenfluramine was also decreased in cortical slices from lithium-treated animals. The sensitivity of the inhibitory 5-HT autoreceptors was assessed by the response to the 5-HT agonist 5-methoxytryptamine. The results indicate a marked reduction in the maximal inhibition of [³H]5-HT release induced by 5-methoxytryptamine in slices obtained from animals which have been treated with lithium for 3 weeks. These data suggest that the functional down regulation of the prejunctional 5-HT sites may be responsible for the increase in K⁺-stimulated 5-HT overflow in brain slices of animals treated chronically with lithium.