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PET Imaging of Dopamine D2 Receptor and Transporter Availability During Acquisition of Cocaine Self-administration in Rhesus Monkeys

Czoty, Paul W. PhD; Gage, H Donald PhD; Nader, Susan H. BA; Reboussin, Beth A. PhD; Bounds, Michael BS; Nader, Michael A. PhD

Journal of Addiction Medicine: March 2007 - Volume 1 - Issue 1 - p 33-39
doi: 10.1097/ADM.0b013e318045c038
Original Article

Previous studies have demonstrated that cocaine use alters availability of brain dopamine D2 receptors (D2R) and transporters (DAT). The present study examined the effects of low doses of cocaine on this neuroadaptation. Using positron emission tomography (PET), D2R and DAT availability in the caudate nucleus (Cd), putamen (Pt), anterior cingulate cortex (ACC), and amygdala (AMY) were assessed before and after monkeys acquired cocaine self-administration. Twelve rhesus monkeys were trained to self-administer intravenous cocaine (0.03 mg/kg per injection) under conditions that resulted in low drug intakes. PET scans using radiotracers targeting D2R ([18F]fluoroclebopride, FCP) or DAT ([18F]-(+)-N-(4-fluorobenzyl)-2β-propanoyl-3β-(4-chlorophenyl)tropane, FCT) were performed when monkeys were cocaine naive and after 9 weeks of self-administration. Before self-administration, D2R availability was significantly higher only in left vs. right Cd, whereas DAT availability was higher in left vs. right Cd, Pt, and ACC. Nonetheless, after cocaine exposure, left-right differences in D2R were apparent in 3 of 4 regions, but only in the ACC for DAT availability. Self-administration of this dose of cocaine did not significantly affect DAT availability in any region and only decreased D2R availability in the ACC. These results demonstrate lateralization of D2R and DAT availability in brain areas that mediate cocaine self-administration, even under conditions in which cocaine does not affect overall receptor availability.

From the Department of Physiology and Pharmacology (PWC, SHN, MAN), Department of Radiology (HDG, MB, MAN), and Department of Biostatistical Sciences (BAR), Wake Forest University School of Medicine, Winston-Salem, NC.

Received December 19, 2006; revised February 3, 2007; accepted February 4, 2007.

Send correspondence and reprint requests to Dr. Michael A. Nader, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, 546 NRC, Winston-Salem, NC 27157-1083. e-mail:

This study was supported by NIDA grants DA 14637 (MAN) and DA 016279 (BAR).

© 2007 American Society of Addiction Medicine