Low level of brain dopamine D₂ receptors in methamphetamine abusers: Association with metabolism in the orbitofrontal cortex

Objective: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D₂ receptors. In cocaine abusers, low levels of D₂ receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers. Method: Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [¹¹C]raclopride to assess the availability of dopamine D₂ receptors and with [¹⁸F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function. Results: Methamphetamine abusers had a significantly lower level of D₂ receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D₂ receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. Conclusions: Lower levels of dopamine D₂ receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D₂ receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D₂ receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.