Glutamatergic metabotropic receptors mGluR1/5: neuroadaptation associated with ethanol behavioral sensitization and self-administration.

Abstract

Only a small percentage of alcohol users become addicted. Addicts have difficulty in changing the focus associated to the drug, perseverate on their abused drugs and struggle to learn new associations. This is due to induction of drastic changes in synaptic plasticity after repeated exposure to drugs, especially in reward systems regions as the Nucleus Accumbens. Changes in the glutamatergic system that induce synaptic plasticity are modulated by metabotropic glutamatergic receptors, possible targets for addiction treatment. The mGluR1/5 receptors are important for ethanol consumption and induction of plasticity. However, little is known about how repeated exposure to ethanol may alter the expression and function of these receptors. In the present study, we intend to use pharmacological, biochemical and electrophysiological techniques to evaluate the expression (western blot) and function (micro-infusion of drugs and/or electrophysiology of slices) of the accumbal mGluR1/5 receptors in mice (Swiss Webster) that developed behavioral sensitization (a form of behavioral adaptation associated with vulnerability to addiction) or that voluntarily consumed ethanol. Considering that not all animals develop sensitization or consume high levels of ethanol, we intend to compare if individual variability in the behavior responses to ethanol is associated with the mGluR1/5 receptors dependent plasticity.