Dopamine D2 Receptor Availability in Opiate-Dependent Subjects before and after Naloxone-Precipitated Withdrawal

Abstract

Dopamine may play a role in opiate withdrawal and dependence. We measured dopamine D₂ receptor availability in 11 opiate-dependent subjects using PET and [¹¹C]raclopride at baseline and during naloxone-precipitated withdrawal. Because [¹¹C]raclopride is sensitive to endogenous dopamine, this strategy enabled us to test whether we could document in humans the DA reductions reported in animal models of opiate withdrawal. Results were compared with values from 11 controls, two of which also received naloxone. The ratio of the distribution volume in striatum to that in cerebellum (B_max/K_d + 1) was used as model parameter for D₂ receptor availability. Baseline measures for B_max/K_d were lower in opiate-dependent subjects (2.44 ± 0.4) than in controls (2.97 ± 0.45, p ≤. 009). Naloxone precipitated an intense withdrawal in the abusers but did not change the B_max/K_d ratio. This study documents decreases in D₂ receptors in opiate-dependent subjects but does not document significant changes in striatal DA concentration during acute withdrawal.