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

Abstract

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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Figure 1: Changes in [18F]FCP DVR as a function of cocaine exposure.
Figure 2: Normalized, coregistered PET images (percent injected dose per cm3) of [18F]FCP binding in the basal ganglia of two representative rhesus monkeys, when cocaine naïve, after approximately 6 months, and after 12 months of cocaine self-administration.
Figure 3: Changes in behavior across one year of food- and cocaine-reinforced responding.
Figure 4: Mean number of reinforcers in the first food component (Fd1) as a function of time over 1 consecutive year of self-administration.

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Acknowledgements

We thank P.W. Czoty, M.L. Banks and K.A. Grant for comments on the manuscript, and C. Hubbard, T. Morton and R. Kuhner for technical assistance. This research was supported by the National Institute on Drug Abuse (grants DA 08468 and DA 14637).

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M.A.N., D.M., S.H.N and T.L.C. contributed to the cocaine self-administration studies; H.D.G., N.B., R.E. and R.H.M. contributed to the PET imaging studies.

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Correspondence to Michael A Nader.

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The authors declare no competing financial interests.

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Nader, M., Morgan, D., Gage, H. et al. PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys. Nat Neurosci 9, 1050–1056 (2006). https://doi.org/10.1038/nn1737

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