Decreased striatal dopaminergic responsivity in alcoholic subjects

Abstract

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Objectives: Alcohol increases extracellular concentration of dopamine (DA) in the nucleus accumbens (NAc), which is an effect associated with the reinforcing effects of drugs but also of natural reinforcers. However, the involvement of DA in alcohol addiction is much less clear. Methods: Here we used PET and [11C]raclopride (D2 receptor radioligand sensitive to competition with endogenous DA) to evaluate reactivity of the DA system, which was measured as changes in specific binding (Bmax’/Kd’) induced by methylphenidate (MP), which is a drug that increases DA by blocking DA transporters. Twenty male alcoholics (41 ±6 years) during early detoxification (1-4 weeks after last alcohol use) and 20 male healthy controls (41 ±6 years), were tested with [11C]raclopride twice 5 minutes before placebo and 5 min after MP (0.5 mg/kg iv). Results: Plasma MP concentrations did not differ between groups. MP-induced significantly greater negative behavioral effects (mood, drug dislike) (p < 0.05) and lower positive effects (drug good, drug liking and high) in alcoholics than controls (p < 0.01). MP significantly decreased Bmax’/Kd’ in caudate (p < 0.001), putamen (p < 0.0001) and ventral striatum (p < 0.001) in both groups. The responses to MP were significantly smaller in alcoholics than in controls in putamen (11% versus 21%; p < 0.03) and in ventral striatum (8% versus 27% p < 0.002). MP-induced DA increases in ventral striatum were correlated with the high and with drug liking (p < 0.05). Conclusions: Decreased DA function in ventral striatum, which is where the NAc is located, is likely to underlie the blunted rewarding responses to MP in alcoholics and may contribute to the anhedonia reported in these patients. This finding is consistent with a prior study (Martinez et al. Biol Psychiatry. 2005) and in addition documents reduced DA function in putamen, which could contribute to movement disorders in alcoholics.