Low Level of Brain Dopamine D2 Receptors in Methamphetamine Abusers: Association With Metabolism in the Orbitofrontal Cortex

ND Volkow, L Chang, GJ Wang… - American Journal of …, 2001 - Am Psychiatric Assoc
ND Volkow, L Chang, GJ Wang, JS Fowler, YS Ding, M Sedler, J Logan, D Franceschi…
American Journal of Psychiatry, 2001Am Psychiatric Assoc
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 …
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.
American Journal of Psychiatry