Chronic lithium treatment enhances the postsynaptic 5-HT1A receptor-mediated 5-HT behavioral syndrome induced by 8-OH-DPAT in rats via catecholaminergic systems.
The effects of antimanic agents, including lithium, carbamazepine, clonazepam and zotepine, on the postsynaptic 5-HT1A receptor-mediated behavioral and hypothermic responses induced by 8-OH-DPAT in rats, and on [3H]8-OH-DPAT binding to 5-HT1A receptors in the rat hippocampus were examined. Treatment with lithium (3 mEq/kg, IP) for 14 days enhanced forepaw treading, one component of the 5-HT behavioral syndrome induced by 8-OH-DPAT, and this enhancement by lithium was abolished by catecholamine depletion with reserpine or alpha-methyl-p-tyrosine, but not by 5-HT depletion with p-chlorophenylalanine. These data suggest that lithium enhances 5-HT1A-mediated behavior via catecholaminergic systems. In contrast, chronic lithium treatment did not alter the hypothermic response to 8-OH-DPAT in untreated rats, as well as in rats treated with reserpine. These findings strengthen the suggestion that lithium has no direct influence on the postsynaptic 5-HT1A-mediated response. Other antimanic agents had no effect on either forepaw treading or hypothermia induced by 8-OH-DPAT. Radioligand binding studies using [3H]-8-OH-DPAT demonstrated that chronic lithium treatment, but not other antimanic agents, caused 5-HT1A receptor down-regulation in rat hippocampus. A discrepancy therefore exists between 5-HT1A receptor down-regulation and unaltered 5-HT1A-mediated behavioral and hypothermic responses in catecholamine-depleted rats after chronic lithium treatment.
Uchitomi
Y
Y
Department of Neurology and Psychiatry, Hiroshima University School of Medicine, Japan.
Yamawaki
S
S
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology; D002395:Catecholamines / Q000502:physiology*; D003988:Dibenzothiepins / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*
D014150:Antipsychotic Agents; D015306:Biogenic Monoamines; D002395:Catecholamines; D003988:Dibenzothiepins; D011985:Receptors, Serotonin; D012701:Serotonin; D002220:Carbamazepine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008094:Lithium; C022172:zotepine