Brain Neurotransmitter Receptor Systems in Alcohol Treated Mice and in Mice Genetically Selected for Differences in Sensitivity to Alcohol

Abstract

The properties of neurotransmitter receptor-effector systems were determined in C57BL/6 mice treated with 7% (v/v) ethanol and in mice selectively bred for differences in sleep time after ethanol administration. Mice treated with ethanol for 7 days and then withdrawn for 24 hours showed a decreased hypothermic response to apomorphine. There was no change in basal or dopamine-stimulated adenylate cyclase activity or in the density or affinity of the receptor for ³H-spiroperidol. A small decrease in the density of β-adrenergic receptors was observed in the cerebral cortex of alcohol-treated and withdrawn mice. This decrease was entirely due to a decrease in the density of β₂-adrenergic receptors. No change was observed in cyclic AMP accumulation due to either α- or β-adrenergic receptor stimulation. Ethanol administration did result in a rapidly reversible increase in the density of muscarinic cholinergic receptors in the hippocampus and cortex.

The properties of neurotransmitter receptors were also determined in mice genetically selected for differences in sensitivity to ethanol. β-Adrenergic receptor density was lower in cortices of long-sleep (LS) mice compared to either short-sleep (SS) mice or to the heterogenous stock (HS). The lower receptor density was tissue specific since no differences in β-adrenergic receptor density were observed in the cerebellum. Cyclic AMP accumulation in response to isoproterenol was not significantly different in the cortex of the three lines of mice. The binding of ³H-spiroperidol in the striatum and of ³H-quinuclidinyl benzilate in cortex, striatum or hippocampus was the same in the three lines of mice. However, dopamine-stimulated adenylate cyclase activity was lower in striata of SS mice.

Supported by Drug Abuse Training Grant (DA 07043) and an Alcohol Research Center (AA03527).