Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers: Implications in addiction

Objective: The authors have shown that decreases in dopamine D₂ receptors in cocaine abusers were associated with decreased metabolism in the cingulate and prefrontal and orbitofrontal cortices. To assess whether increasing dopamine would reverse these metabolic decrements, they measured the effects of methylphenidate, a drug that increases dopamine, on brain glucose metabolism in 20 cocaine abusers. Method: The subjects underwent two [¹⁸F]fluorodeoxyglucose positron emission tomography scans, one after two sequential placebo injections and one after two intravenous doses of methylphenidate. D₂ receptors were measured with [¹¹C]raclopride to evaluate their relation to methylphenidate-induced metabolic changes. Results: Methylphenidate induced variable changes in brain metabolism: subjects with the higher D₂ measures tended to increase metabolism, whereas those with the lower D₂ measures tended to decrease metabolism. Methylphenidate's effects were significant for increases in metabolism in the superior cingulate, right thalamus, and cerebellum. Methylphenidate-induced changes in the right orbitofrontal cortex and right striatum were associated with craving, and those in the prefrontal cortex were associated with mood. Conclusions: Although methylphenidate increased metabolism in the superior cingulate, it only increased metabolism in orbitofrontal or prefrontal cortices in the subjects in whom it enhanced craving and mood, respectively. This indicates that dopamine enhancement is not sufficient per se to increase metabolism in these frontal regions. Activation of the right orbitofrontal cortex and right striatum (brain regions found to be abnormal in compulsive disorders) in the subjects reporting craving may be one of the mechanisms underlying compulsive drug administration in addicted persons. The predominant correlation of craving with right but not left brain regions suggests laterality of reinforcing and/or conditioned responses.