Chronic lithium: desensitization of autoreceptors mediating serotonin release.

The effect of chronic lithium treatment on K+-induced release of preloaded [3H] serotonin [( 3H]5-HT) from brain slices and its regulation by the presynaptic serotonin autoreceptors were investigated in superfused cortical, hippocampal and hypothalamic brain slices. Three weeks of treatment with a lithium-containing diet increased stimulation-induced [3H]5-HT overflow in the three brain regions examined. The sensitivity of the inhibitory serotonin autoreceptors was tested by determining K+-elicited release inhibition or potentiation in response to exposure to the agonist, LSD or to the antagonist, methiothepin, respectively. A reduced maximal inhibitory response to LSD was obtained in lithium-treated animals. The potentiation by methiothepin was also markedly diminished in the treated animals. These results suggest that chronic lithium treatment induces a desensitization of serotonin autoreceptors which may result in increased serotonin release from the serotonin nerve terminals.