An Altered Pattern of Neurotransmitter Receptor Expression Emerges during Adolescent Alcohol Consumption

Abstract

Adolescent rats develop a severe alcohol withdrawal syndrome when fed alcohol as part of a liquid diet. The present study sought to correlate quantitative changes in neurotransmitter receptors with the severity of alcohol withdrawal symptoms. Membranes were isolated from brain fractions from rats fed an alcohol‐containing liquid diet beginning at P28 and continuing on into the adolescent period. Membranes were probed for specific receptors by Western blotting. During the period of up to 10 days, excitatory glutamate receptors (both AMPA and NMDA subtypes) increase significantly. This up regulation of glutamate receptors coincides with a time when the primary withdrawal behavior is anxiety‐like. By 14 days, adenosine A1 receptors decline significantly reaching a level 50% of that of pair‐fed controls. There are no corresponding changes in adenosine A2a receptors. Down regulation of A1 coincides with a time when 90% of the rats experience convulsions upon alcohol withdrawal. A detergent resistant (raft) fraction was isolated from brain membranes to determine which of these receptors may be located in lipid rafts. Initial analyses indicate all 3 receptors of interest are at least partially localized to lipid rafts. We conclude that the most severe alcohol withdrawal symptoms may occur in adolescents when up regulation of excitatory glutamate receptors coincides with down regulation of A1 receptors and thus with loss of the ‘brakes’ adenosine might normally apply to the glutamate system. Further studies will explore the potential role of lipid raft dynamics in these changes.