Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec.
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec; Department of Psychiatry, McGill University, Montreal, Quebec.
Biol Psychiatry. 2014 Jul 1;76(1):23-30. doi: 10.1016/j.biopsych.2013.08.033. Epub 2013 Oct 17.
Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses.
We measured amphetamine-induced changes in [(11)C]raclopride binding in 1) high-risk young adults with a multigenerational FH of substance use disorders (n = 16); 2) stimulant drug-naïve healthy control subjects with no known risk factors for addiction (n = 17); and 3) subjects matched to the high-risk group on personal drug use but without a FH of substance use problems (n = 15).
Compared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [(11)C]raclopride responses, particularly within the right ventral striatum. Past drug use predicted the dopamine response also, but including it as a covariate increased the group differences.
Together, the results suggest that young people at familial high risk for substance use disorders have decreased dopamine responses to an amphetamine challenge, an effect that predates the onset of addiction.
并非每个尝试成瘾药物的人都会发展出物质使用障碍。风险的最佳预测因素之一是物质使用问题的家族史 (FH)。部分原因可能反映了中脑边缘多巴胺反应的紊乱。
我们测量了 1) 有多代物质使用障碍 FH 的高风险年轻成年人（n = 16）；2) 无已知成瘾风险因素的兴奋剂药物-naïve 健康对照受试者（n = 17）；和 3) 在个人用药方面与高风险组相匹配但无物质使用问题 FH 的受试者（n = 15）对安非他命诱导的 [(11)C]raclopride 结合的变化。
与任何对照组相比，有多代物质使用障碍 FH 的高风险年轻成年人的 [(11)C]raclopride 反应较小，尤其是右侧腹侧纹状体。过去的药物使用也预测了多巴胺反应，但将其作为协变量包括在内会增加组间差异。
综上所述，结果表明，有物质使用障碍家族高风险的年轻人对安非他命挑战的多巴胺反应降低，这种效应先于成瘾的发生。
