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

Background: A decrease in dopamine type 2 receptors (D₂) and mesolimbic dopamine transmission predisposes animals to consume alcohol. This study measured D₂ receptors and dopamine transmission in human alcohol-dependent (AD) subjects using positron emission tomography (PET) and [¹¹C]raclopride. Methods: Fifteen AD and 15 healthy control (HC) subjects were scanned before and after a psychostimulant challenge (amphetamine .3 mg/kg intravenous). The outcome measures for baseline D₂ receptor availability were binding potential (BP) and the equilibrium partition coefficient (V₃″). Amphetamine-induced [¹¹C] raclopride displacement was measured as the difference in V₃″ between the two scans. Results: [¹¹C]raclopride BP was significantly 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 striatum: [¹¹C]raclopride displacement was -5.2% ± 3.6% in AD subjects compared with -13.0% ± 8.8% in HC. However, no significant difference in [¹¹C]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 D₂ receptors in each striatal subdivision, whereas amphetamine-induced dopamine release was reduced in the limbic striatum only.