Effect of lithium carbonate on the enhancement of serotonin 2A receptor elicited by dexamethasone.
The purpose of this study was to investigate whether chronic dexamethasone (Dex) administration induces serotonin (5-HT) 2A receptor supersensitivity and if chronic lithium carbonate (Li) administration contributes to the normalization of 5-HT2A receptor supersensitivity induced by Dex in rat brain. We investigated the effects of a 14-day administration of Dex and/or Li on changes in body weight (BW), on plasma corticosterone levels, on plasma lithium levels, on 5-HT2A receptor binding sites, and on (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI)-induced wet dog shake (WDS), which is mediated by 5-HT2A receptor in rats. Dex significantly reduced the BW of rats. Li did not have any effect on BW gain and did not prevent the BW loss induced by Dex. The plasma corticosterone levels of rats treated with Dex were too low to be detected. Li did not have any effect on corticosterone levels and did not prevent the decrease in the corticosterone levels induced by Dex. Six hours after the last treatment, the plasma lithium levels of rats treated with Li were significantly higher than those of rats treated with Dex/Li. Chronic Dex administration resulted in a significant increase in the density (B(max)) of the 5-HT2A receptor without a significant change in the affinity (K(d)). The increase in the B(max) induced by Dex was not prevented by chronic combined treatment with Dex and Li. Chronic Dex administration potentiated the WDS, and this increase was prevented by chronic combined treatment with Dex and Li. Chronic Li administration did not have any effect on WDS. These results indicate that chronic Li administration may improve the supersensitivity of the 5-HT2A receptor elicited by chronic Dex administration without decreasing the density of the 5-HT2A receptor, and the effect of Li was also independent of hypothalamo-pituitary-adrenal axis function.
Jitsuiki
H
H
Department of Psychiatry and Neurosciences, Hiroshima University, School of Medicine, Hiroshima, Japan.
Kagaya
A
A
Goto
S
S
Horiguchi
J
J
Yamawaki
S
S
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004357:Drug Synergism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D016651:Lithium Carbonate / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D019579:Neocortex / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D018692:Antimanic Agents; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D016651:Lithium Carbonate; D003345:Corticosterone