Alterations in serotonin receptor subtypes in ethanol-dependent rats.
Serotonin (5-HT) receptor subtypes were investigated during severe ethanol intoxication and withdrawal. Ethanol was administered intragastrically five times a day for 4 days (12 g/kg per day). 5-HT receptor subtypes were studied: (1) in severely intoxicated animals (mean blood ethanol concentration (BEC) = 4.7 g/l); (2) during the withdrawal reaction; and (3) in a control group. The maximal density of [3H] 8-hydroxy-2-(di-n- propylamino)tetralin [( 3H] 8-OH-DPAT) binding (Bmax) to 5-HT1a receptors was decreased by 25 and 17% in the hippocampus during chronic ethanol intoxication and withdrawal, respectively. [3H]Ketanserin binding to 5-HT2 receptors in the cortex, (-)[125I]-iodo-cyanopindolol [( 125I]CYP) binding to 5-HT1b receptors in the striatum and hypothalamus, and [3H] 8-OH-DPAT binding in the cortex were not affected by chronic ethanol administration. Previous in vitro experiments have shown that 5-HT1a receptors in the hippocampus are inhibitory. The down-regulation of these receptors may play a role in physical ethanol dependence, by inducing hyperexcitability of the hippocampus.
Ulrichsen
J
J
Laboratory of Clinical Psychopharmacology, National Institute on Drug Abuse, Baltimore, MD 21224.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000430:Alcohol Withdrawal Delirium / Q000503:physiopathology*; D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D000431:Ethanol / Q000493:pharmacokinetics; D007650:Ketanserin / Q000493:pharmacokinetics; D010869:Pindolol / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000145:classification* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D000431:Ethanol; C047975:cyanopindolol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D010869:Pindolol