Michael A Nader1, Paul W Czoty. 1. 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
Abstract
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. METHOD: 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.
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. METHOD: 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.
Authors: Fernando Caravaggio; Jun Ku Chung; Philip Gerretsen; Gagan Fervaha; Shinichiro Nakajima; Eric Plitman; Yusuke Iwata; Alan Wilson; Ariel Graff-Guerrero Journal: Soc Neurosci Date: 2016-02-29 Impact factor: 2.083