Effect of Ethanol Administration and Withdrawal on Serotonin Receptor Subtypes and Receptor‐Mediated Phosphoinositide Hydrolysis in Rat Brain

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Abstract
The effect of short‐term (15 days) and long‐term (60 days) ethanol treatment and withdrawal on agonist‐stimulated phosphoinositide (PI) hydrolysis, serotonin receptor subtypes (5HT1A and 5HT2), and α1‐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‐l‐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 KD1 as well as a decrease in 5HT‐stimulated [3H].IP1 formation in rat cerebral cortex. 5HT1A and α1‐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 5HT21, 5HT1A, and α1‐ adrenergic receptors, as well as NE and A23187‐stimulated [3H]‐IP1 formation, but significantly decreased the 5HT‐stimulated [3H]‐IPl 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.