PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys

Michael A Nader^1, 2, Drake Morgan^1, 3, H Donald Gage², Susan H Nader¹, Tonya L Calhoun¹, Nancy Buchheimer², Richard Ehrenkaufer² &  Robert H Mach^1, 2, 3

¹  Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.

²  Department of Radiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.

³  Present addresses: Department of Psychiatry, Division of Addiction Medicine, University of Florida, College of Medicine, Gainesville, Florida 32610, USA (D.M.) and Division of Radiological Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA (R.H.M.).

Dopamine neurotransmission is associated with high susceptibility to cocaine abuse. Positron emission tomography was used in 12 rhesus macaques to determine if dopamine D2 receptor availability was associated with the rate of cocaine reinforcement, and to study changes in brain dopaminergic function during maintenance of and abstinence from cocaine. Baseline D2 receptor availability was negatively correlated with rates of cocaine self-administration. D2 receptor availability decreased by 15–20% within 1 week of initiating self-administration and remained reduced by 20% during 1 year of exposure. Long-term reductions in D2 receptor availability were observed, with decreases persisting for up to 1 year of abstinence in some monkeys. These data provide evidence for a predisposition to self-administer cocaine based on D2 receptor availability, and demonstrate that the brain dopamine system responds rapidly following cocaine exposure. Individual differences in the rate of recovery of D2 receptor function during abstinence were noted.

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