17332017 - Psychopharmacology (2005) 180: 473490 DOI

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Psychopharmacology (2005) 180: 473 490 DOI 10.1007/s00213-005-2180-z ORIGINAL INVESTIGATION Serge H. Ahmed . George F. Koob Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function Received: 28 August 2004 / Accepted: 9 January 2005 / Published online: 25 February 2005 # Springer-Verlag 2005 Abstract Rationale: The transition from initial drug use to drug addiction has been proposed to result from an allostatic decrease in reward function driven by an over- activation of brain antireward processes. Objectives: How decreased reward function explains compulsive drug use is not entirely clear at present, and is still a subject for debate. Methods: We present a quantitative model of cocaine self- administration that integrates pharmacokinetic, pharmaco- dynamic, and motivational factors to address this question. The model assumes that reward system responsivity is a homeostatically regulated process where the desired level of responsivity (called the reward set point) is initially dif- ferent from the baseline level. The reduction or correction of this difference or error in reward function would drive cocaine self-administration. Results: Theoretical data ob- tained by computer simulation fit the experimental data obtained in animals self-administering cocaine (i.e., the within- session pattern of self-injections, the shape and curvature of the dose-injection function, the nonlinear relationship be- tween drug intake and regulated drug effects). Important- ly, simulation of an allostatic decrease in reward system responsivity exacerbates the initial error that drives self- administration, thereby increasing both the intake of, and the motivation for, the drug. This allostatic change mani- fests as a vertical shift in the dose-injection function similar to that seen in animals with escalating cocaine self-admin- istration. Conclusions: The present model provides a sat- isfactory explanation of escalated drug intake and suggests a novel negative reinforcement view of addiction based on an allostatic decrease in reward function. Keywords Reward . Reinforcement . Self-administration . Self-medication . Self-regulation . Dopamine . Cocaine . Laboratory environment Introduction Escalation of drug consumption marks the transition from drug use to drug addiction. This process of escalation is exceptionally well illustrated in an old clinical study by Abraham Wikler ( 1952 ). An abstinent subject with a his- tory of opiate use was given ad libitum access to intrave- nous morphine during a period of 4 months. His morphine intake dramatically escalated between days from an initial level of 60 mg day - 1 to a final level of more than 1,000 mg day - 1 . Escalation of drug use in response to increased drug availability occurs also with stimulant drugs (Siegel 1984 ; White 1988 ; Gawin and Ellinwood 1989 ; Ferri et al. 2001 ).
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This note was uploaded on 10/16/2011 for the course PSYCH 101 taught by Professor Brown,b during the Spring '08 term at BYU.

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17332017 - Psychopharmacology (2005) 180: 473490 DOI

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