title: Effect of ethanol administration and withdrawal on serotonin receptor subtypes and receptor-mediated phosphoinositide hydrolysis in rat brain.
abstract: The effect of short-term (15 days) and long-term (60 days) ethanol treatment and withdrawal on agonist-stimulated phosphoinositide (Pl) hydrolysis, serotonin receptor subtypes (5HT1A and 5HT2), and alpha 1-adrenergic receptors were studied in rat cerebral cortex. Short-term ethanol treatment had no significant effect on serotonin (5HT), norepinephrine (NE), and calcium ionophore (A23187)-stimulated [3H]-inositol-1-phosphate ([3H]-IP1) formation and 5-HT2 receptors as measured by 125I-lysergic acid diethylamide (125I-LSD) binding, in rat cerebral cortex. However, 15 days of ethanol treatment, followed by 24 hr of withdrawal resulted in a decrease in Bmax of 125I-LSD binding without significant change in KD, as well as a decrease in 5HT-stimulated [3H]-IP1 formation in rat cerebral cortex. 5HT1A and alpha 1-adrenergic receptors were determined by using [3H]-8-hydroxy-2-(di-N-propylamino)tetralin and [3H]-prazosin as radioligand, respectively. We also observed that long-term ethanol treatment had no significant effect on Bmax and KD of 5HT2, 5HT1A, and alpha 1-adrenergic receptors, as well as NE and A23187-stimulated [3H]-IP1 formation, but significantly decreased the 5HT-stimulated [3H]-IP1 formation in rat cerebral cortex. It is possible that a decrease in 5HT-induced PI turnover after long-term ethanol exposure may be due to a decrease in coupling of 5HT2 receptors to G protein or PLC enzyme, whereas the decrease in 5HT-induced PI turnover after withdrawal may be due to a decrease in functional 5HT2 receptor number.
authors.affiliation: Illinois State Psychiatric Institute, Chicago 60651.
authors.forename: S C
authors.initials: SC
authors.lastname: Pandey
authors.forename: M R
authors.initials: MR
authors.lastname: Piano
authors.forename: D W
authors.initials: DW
authors.lastname: Schwertz
authors.forename: J M
authors.initials: JM
authors.lastname: Davis
authors.forename: G N
authors.initials: GN
authors.lastname: Pandey
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000493:pharmacokinetics; D000430:Alcohol Withdrawal Delirium / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006868:Hydrolysis; D008238:Lysergic Acid Diethylamide / Q000493:pharmacokinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011224:Prazosin / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000145:classification / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D010716:Phosphatidylinositols; D011941:Receptors, Adrenergic; D011985:Receptors, Serotonin; D012701:Serotonin; D000001:Calcimycin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008238:Lysergic Acid Diethylamide; D009638:Norepinephrine; D011224:Prazosin