Imaging of dopamine D2/3 agonist binding in cocaine dependence: a [11C]NPA positron emission tomography study

Objective: Positron emission tomography (PET) studies performed with [¹¹C]raclopride have consistently reported lower binding to D_2/3 receptors and lower amphetamine‐induced dopamine (DA) release in cocaine abusers relative to healthy controls. A limitation of these studies that were performed with D_2/3 antagonist radiotracers such as [¹¹C]raclopride is the failure to provide information that is specific to D_2/3 receptors configured in a state of high affinity for the agonists (i.e., D_2/3 receptors coupled to G‐proteins, D_{2/3 HIGH}). As the endogenous agonist DA binds with preference to D_{2/3 HIGH} relative to D_{2/3 LOW} receptors (i.e., D_2/3 receptors uncoupled to G‐proteins) it is critical to understand the in vivo status of D_{2/3 HIGH} receptors in cocaine dependence. Thus, we measured the available fraction of D_{2/3 HIGH} receptors in 10 recently abstinent cocaine abusers (CD) and matched healthy controls (HC) with the D_2/3 antagonist and agonist PET radiotracers [¹¹C]raclopride and [¹¹C]NPA. Methods: [¹¹C]raclopride and [¹¹C]NPA binding potential (BP) (BP_ND) in the striatum were measured with kinetic analysis using the arterial input function. The available fraction of D_{2/3 HIGH} receptors, i.e., % R_HIGH available = D_{2/3 HIGH}/(D_{2/3 HIGH} + D_{2/3 LOW}) was then computed as the ratio of [¹¹C]NPA BP_ND/[¹¹C]raclopride BP_ND. Results: No differences in striatal [¹¹C]NPA BP_ND (HC = 1.00 ± 0.17; CD = 0.97 ± 0.17, P = 0.67) or available % R_HIGH (HC = 39% ± 5%; CD = 41% ± 5%, P = 0.50) was observed between cocaine abusers and matched controls. Conclusions: The results of this [¹¹C]NPA PET study do not support alterations in D_{2/3 HIGH} binding in the striatum in cocaine dependence. Synapse, 2011. © 2011 Wiley‐Liss, Inc.