Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum

Background: A decrease in dopamine type 2 receptors (D-2) and mesolimbic dopamine transmission predisposes animals to consume alcohol. This study measured D-2 receptors and dopamine transmission in human alcohol-dependent (AD) subjects using positron emission tomography (PET) and [C-11]raclopride. Methods: Fifteen AD and 15 healthy control (HC) subjects were scanned before and after a psychostimulant challene (amphetamine 3 mg/kg intravenous). The outcome measures for baseline D-2 receptor availability were binding potential (BP) and the equilibrium partition coefficient (V-3 ''). Amphetamine-induced [C-11]raclopride displacement was measured as the difference in V-3 '' between the two scans. Results: [C-11]raclopride BP was signifcantly reduced by 16.6% in the limbic striatum, 19.2% in the associative striatum, and 21.3% in the sensorimotor striatum in AD subjects compared with HC. The alcohol-dependent subjects showed a blunting of amphetamine-induced dopamine release in the limbic straitum: [C-11]raclopride displacement was -5.2% +/- 3.6% in AD subjects compared with -13.0% +/- 8.8% in HC. However, no significant difference in [C-11]raclopride displacement was seen in the associative (-4.6% +/- 5.8% in AD subjects vs. -6.7 +/- 5.4% in HC) and sensorimotor (-12.3% +/- 7.3% in AD subjects vs. -13.7% +/- 7.5% in HC) subdivisions of the striatum between the two groups. Conclusions: Alcohol dependence was associated with a decrease in D-2 receptors in each straital subdivision, whereas amphetamine-induced dopamine release was reduced in the limbic striatum only.