Effect of chronic lithium treatment on 5-hydroxytryptamine autoreceptors and release of 5-[3H]hydroxytryptamine from rat brain cortical, hippocampal, and hypothalamic slices.
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 but not in hippocampus [corrected]. 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.
Friedman
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Department of Psychiatry and Pharmacology, Medical College of Pennsylvania at Eastern Pennsylvania Psychiatric Institute, Philadelphia 19129.
Wang
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D008735:5-Methoxytryptamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology*; D005277:Fenfluramine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
D002712:Chlorides; D011985:Receptors, Serotonin; D005277:Fenfluramine; D012701:Serotonin; D008735:5-Methoxytryptamine; D008719:Methiothepin; D008094:Lithium; D018021:Lithium Chloride; D011188:Potassium; D002118:Calcium