Alcohol Dependence Is Associated with Blunted Dopamine Transmission in the Ventral Striatum

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• 作者：Diana Martinez ; Roberto Gil ; Mark Slifstein ; Dah-Ren Hwang ; Yiyun Huang ; Audrey Perez ; Lawrence Kegeles ; Peter Talbot ; Suzette Evans ; John Krystal et al.
• 刊名：Biological Psychiatry
• 出版年：2005
• 出版时间：15 November 2005
• 年：2005
• 卷：58
• 期：10
• 页码：779-786
• 全文大小：242 K

文摘

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.