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.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*
D011985:Receptors, Serotonin; D008719:Methiothepin; D008238:Lysergic Acid Diethylamide; D008094:Lithium; D011188:Potassium