Brain neurotransmitter receptor systems in mice genetically selected for differences in sensitivity to ethanol

The density of receptors for neurotransmitters and receptor-mediated cellular responsiveness were determined in tissues from two lines of mice selectively bred for differences in sleep time after ethanol administration. The studies were undertaken to ascertain in differences in neurotransmitter receptors between the lines might explain any of the differences seen in initial sensitivity to ethanol. The results were compared with those obtained in studies using the parent heterogeneous stock (HS). The animals used in the current experiments did not receive ethanol. β-Adrenergic receptor density, as measured by the binding of (¹²⁵I)-iodohydroxybenzylpindolol, was lower in cortices of alcohol-sensitive long-sleep mice (LS) as compared to the short-sleep (SS) animals or to HS controls. The densities of β₁ and β₂-adrenergic receptors were lower by approximately the same amount. The results were tissue specific in that there was no difference in the density of β-adrenergic receptors in the cerebellum. Cyclic AMP accumulation in response to isoproterenol was not significantly different in the cortex of LS mice despite the decrease in β-adrenergic receptors. No differences were found in ³H-spiroperidol binding to dopamine receptors in the striatum or in ³H-quinuclidinylbenzilate binding to muscarinic cholinergic receptors in the cortex, striatum or hippocampus. Dopamine-stimulated adenylate cyclase activity was, how- ever, lower in striata of SS mice. The affinities of the receptors for the various ligands studied were the same in the three lines of mice.