PET imaging of dopamine D2 receptors in monkey models of cocaine abuse: genetic predisposition versus environmental modulation.
OBJECTIVE
Animals self-administer many of the drugs that humans abuse, including cocaine. This article describes studies using preclinical animal models to differentiate the influences of neurobiological predisposition from environmental modulation of cocaine addiction, including studies from the authors' laboratory using nonhuman primates.


METHODS
Addiction is described in terms of vulnerability, maintenance, and abstinence. This review focuses on dopamine receptor function, in particular that of the D2-like receptors, as measured by the noninvasive imaging procedure positron emission tomography. Findings from human studies of addiction and animal models are reviewed.


RESULTS
There appears to be an inverse relationship between D2 receptor availability and vulnerability to the reinforcing effects of cocaine. Environmental variables can increase or decrease D2 receptor binding in an orderly fashion, and the resulting changes in D2 function influence the vulnerability to abuse cocaine. In maintenance, chronic cocaine exposure produces decreases in D2 receptor binding, which may be a mechanism that contributes to continued drug use. Finally, during abstinence there are individual differences in rates of recovery of D2 receptor availability.


CONCLUSIONS
The goal of the preclinical research described in this review is to achieve a better understanding of individual differences in susceptibility and vulnerability to the reinforcing effects of cocaine. It is clear that the development of novel animal models will extend our understanding of the neurobiological basis of drug addiction to include a greater appreciation of the role of environmental factors in affecting predisposition, mediating continued drug use, and triggering relapse.
Nader
Michael A
MA
Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. mnader@wfubmc.edu
Czoty
Paul W
PW
D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D016739:Behavior, Addictive / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001549:Benzamides; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics; D000882:Haplorhini; D006801:Humans; D010880:Piperidines; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012930:Social Dominance; D012931:Social Environment
D001549:Benzamides; D010880:Piperidines; D017448:Receptors, Dopamine D2; C083673:fluoroclebopride; D020891:Raclopride