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Animal Models of Drug Dependence: Motivational Perspective

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Addiction Medicine

Abstract

Drug addiction, also known as substance Dependence, is a chronically relapsing disorder characterized by (i) compulsion to seek and take the drug, (ii) loss of control in limiting intake, and, as defined by the present author, (iii) emergence of a negative emotional state (e.g., dysphoria, anxiety, or irritability) when access to the drug is prevented (defined here as dependence with a lower case “d”). A composite addiction cycle comprising three stages—preoccupation/anticipation, binge/intoxication, and withdrawal/negative affect—in which negative reinforcement and compulsivity dominate the terminal stages, is proposed to account for many of the symptoms of addiction. The purpose of this review is to focus on the role of animal models of the negative emotional state of the withdrawal/negative affect stage of the addiction cycle that have relevance to the motivational changes driving the compulsivity of addiction. Animal models of dependence are explored in the context of face and construct validity and include models for the negative emotional state of acute withdrawal (e.g., anxiety-like measures, aversive-like responses, and increases in reward thresholds) and models of excessive drug intake driven by dependence (e.g., extended-access self-administration and withdrawal-induced drinking). Neuropharmacological substrates for the negative emotional states and excessive drug seeking associated with dependence are hypothesized to include decreases in reward function, recruitment of brain stress (or anti-reward) systems, and dysregulation of anti-stress systems. Animal models of excessive drug intake associated with negative reinforcement provide a novel perspective on addiction and novel targets for restoring motivational homeostasis in addiction.

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Acknowledgements

Supported by the Pearson Center for Alcoholism and Addiction Research and National Institutes of Health grants AA06420 and AA08459 from the National Institute on Alcohol Abuse and Alcoholism, DA04043 and DA04398 from the National Institute on Drug Abuse, and DK26741 from the National Institute of Diabetes and Digestive and Kidney Diseases. The author would like to thank Michael Arends for his assistance with manuscript preparation.

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  1. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, 92037, USA

    George F. Koob

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  1. , Depts Psychiat & Neurobehav Sciences, Me, University of Virginia, Charlottesville, 22908, Virginia, USA

    Bankole A. Johnson

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Koob, G.F. (2010). Animal Models of Drug Dependence: Motivational Perspective. In: Johnson, B. (eds) Addiction Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0338-9_15

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