EFFECTS OF ETHANOL ADMINISTRATION AND WITHDRAWAL ON NEUROTRANSMITTER RECEPTOR SYSTEMS IN C57 MICE

Abstract

C57BL/6 mice were treated with 7% (vol/vol) ethanol in a BioServe liquid diet for 7 days. Some animals were allowed to withdraw from ethanol for a period of 24 h. The severity of the ethanol withdrawal was assessed by monitoring behavioral changes and by quantitating the decrease in body temperature that occurred during the first 16 h of withdrawal. Animals withdrawn from ethanol for 24 h showed a decreased hypothermic response to apomorphine, suggesting that changes in dopaminergic systems had occurred. This possibility was examined in homogenates of striatum by measuring dopamine-stimulated adenylate cyclase activity and the binding of [3H]spiroperidol. There were no changes observed in basal- or dopamine-stimulated adenylate cyclase activity or in the density or affinity of receptors for [3H]spiroperidol. The affinity of apomorphine for the dopamine receptor was unchanged. .alpha. and .beta. adrenergic receptor-mediated increases in cyclic[c]AMP accumulation were assessed in slices of cerebral cortex. There was no change in cAMP accumulation due to .alpha. or .beta. adrenergic receptors. There was a significant decrease in the density of .beta. adrenergic receptors in both the ethanol-treated mice and in the withdrawn mice. This decrease was restricted to the .beta.-2 receptor subtype with no change in the density of .beta.-1 adrenergic receptors. Ethanol administration was associated with a significant increase in the density of muscarinic cholinergic receptors in the hippocampus and cerebral cortex. The effect was not observed in animals allowed to withdraw for 24 h.