Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement - PubMed (original) (raw)

Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement

Nora D Volkow et al. J Neurosci. 2007.

Abstract

The value of rewards (natural rewards and drugs) is associated with dopamine increases in the nucleus accumbens and varies as a function of context. The prefrontal cortex has been implicated in the context dependency of rewards and in the fixated high value that drugs have in addiction, although the mechanisms are not properly understood. Here we test the hypothesis that the prefrontal cortex regulates the value of rewards by modulating dopamine increases in nucleus accumbens and that this regulation is disrupted in addicted subjects. We used positron emission tomography to evaluate the activity of the prefrontal cortex (measuring brain glucose metabolism with [18F]fluorodeoxyglucose) and dopamine increases (measured with [11C]raclopride, a D2/D3 receptor ligand with binding that is sensitive to endogenous dopamine) induced by the stimulant drug methylphenidate in 20 controls and 20 detoxified alcoholics, most of whom smoked. In all subjects, methylphenidate significantly increased dopamine in striatum. In ventral striatum (where the nucleus accumbens is located) and in putamen, dopamine increases were associated with the rewarding effects of methylphenidate (drug liking and high) and were profoundly attenuated in alcoholics (70 and 50% lower than controls, respectively). In controls, but not in alcoholics, metabolism in orbitofrontal cortex (region involved with salience attribution) was negatively associated with methylphenidate-induced dopamine increases in ventral striatum. These results are consistent with the hypothesis that the orbitofrontal cortex modulates the value of rewards by regulating the magnitude of dopamine increases in the ventral striatum and that disruption of this regulation may underlie the decreased sensitivity to rewards in addicted subjects.

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Figures

Figure 1.

Figure 1.

Average for the DV ratio (DVR) images for [11C]raclopride for the controls (n = 20) and the alcoholics (n = 20) at the level of striatum after placebo and after MP. Note the decrease in specific binding (DV ratios) with MP and the attenuated response to MP in alcoholic subjects compared with the controls.

Figure 2.

Figure 2.

Regression slopes between percentage changes in _B_max′/_K_d′ (dependent variable) in VS and absolute regional brain metabolic activity in OFC (BA 11), anterior CG (BA 32), and DLPFC (BA 9) in controls (filled circles) and in alcoholics (open circles). Note that percentage decreases in the specific binding of [11C]raclopride (_B_max′/_K_d′) reflect relative DA increases, and thus the regression conveys a negative correlation: the lower the metabolism, the greater the DA increases.

Figure 3.

Figure 3.

Regression slopes between percentage changes in _B_max′/_K_d′ (dependent variable) in VS and normalized metabolic activity in OFC (whole brain) in controls (filled circles) and in alcoholics (open circles).

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