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Background: 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. Methods: We measured amphetamine-induced changes in [11C]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). Results: Compared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [11C]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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: The effect of self-administered cocaine on extracellular dopamine (DA) levels has not been measured in humans. Methods: Ten nondependent cocaine users underwent positron emission tomography [11C]raclopride scans following intranasal self-administration of cocaine hydrochloride (1.0 mg/kg) and placebo powder. Results: Compared with placebo, intranasal cocaine self-administration decreased [11C]raclopride binding values in the ventral limbic striatum and putamen. Individual differences in the magnitude of the [11C]raclopride response in the ventral striatum were predicted by lifetime histories of stimulant drug use. Conclusions: The results suggest that 1) intranasal cocaine self-administration increases synaptic DA levels in human striatum and 2) prior use of stimulant drugs on the street is associated with progressively greater cocaine-induced DA responses. These dopaminergic effects might influence susceptibility to drug–seeking behavior and the progression to substance abuse. [Copyright &y& Elsevier]