Editors' ChoiceAddiction

Souse the mouse

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Science Translational Medicine  02 Sep 2015:
Vol. 7, Issue 303, pp. 303ec150
DOI: 10.1126/scitranslmed.aad1828

Alcohol is the most common drug of abuse, and the U.S. Centers for Disease Control and Prevention estimates that excessive alcohol intake is responsible for 88,000 deaths per year in the United States. Behavioral interventions are the mainstay for alcohol dependence treatment, and existing medications have modest efficacy at best and are rarely used.

In a recent study, Wang and colleagues investigated the dorsomedial striatum, a brain region important in reward-directed behaviors, in a mouse model of alcohol use. The dorsomedial striatum primarily consists of neurons that express either dopamine receptor type 1 (DR1) or dopamine receptor type 2 (D2R). In the first experiment, daily doses of intraperitoneal alcohol increased AMPA-induced currents in D1R-expressing neurons, but not in D2R-expressing neurons. The investigators developed a new strain of mouse through crossbreeding that consumed higher quantities of alcohol (16 versus 5 g/kg/day). Following 8 weeks of intermittent heavy alcohol use—in a model of excessive consumption and withdrawal in which there was 24 hours of access to alcohol on each Monday, Wednesday, and Friday—the authors observed increased AMPA-induced currents in the D1R-expressing neurons of the dorsomedial striatum but saw no change in the D2R-expressing neurons. Morphological examination revealed an increase in dendritic arborization and the density of mature dendritic spines in D1R-expressing neurons, but not in D2R-expressing neurons. Infusion of a D1R antagonist called SCH 23390 reduced alcohol intake, whereas a D2R antagonist did not affect alcohol intake.

These results imply that alcohol intake induces morphological changes in D1R-expressing neurons and increases D1R-mediated synaptic activity, which increases alcohol-seeking behaviors, and that blocking D1R decreases alcohol intake. Prior studies have examined the contribution of dopamine pathways to alcohol intake in animal models and in humans. However, they have primarily focused on D2R-mediated pathways, or have used medications that nonselectively affect D1R, D2R, and other dopamine receptor activity. This study suggests that specifically targeting D1R is a better strategy for a more effective medical treatment of alcohol abuse.

J. Wang, et al., Alcohol elicits functional and structural plasticity selectively in dopamine D1 receptor-expressing neurons of the dorsomedial striatum. J. Neurosci. 35, 11634–11643 (2015). [Abstract]

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