title: Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function.
abstract: BACKGROUND
  The transition from initial drug use to drug addiction has been proposed to result from an allostatic decrease in reward function driven by an overactivation of brain antireward processes.
  
  
  OBJECTIVE
  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, pharmacodynamic, 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 different from the baseline level. The reduction or correction of this difference or error in reward function would drive cocaine self-administration.
  
  
  RESULTS
  Theoretical data obtained 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 between drug intake and regulated drug effects). Importantly, 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 manifests as a vertical shift in the dose-injection function similar to that seen in animals with escalating cocaine self-administration.
  
  
  CONCLUSIONS
  The present model provides a satisfactory explanation of escalated drug intake and suggests a novel negative reinforcement view of addiction based on an allostatic decrease in reward function.
authors.affiliation: Laboratoire de Neuropsychobiologie des Désadaptations, University Victor-Segalen Bordeaux2, CNRS-UMR 5541, 33076, Bordeaux, France. sahmed@lnpb.u-bordeaux2.fr
authors.forename: Serge H
authors.initials: SH
authors.lastname: Ahmed
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000222:Adaptation, Physiological; D000465:Algorithms; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000493:pharmacokinetics; D003198:Computer Simulation; D016571:Neural Networks, Computer; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration; D019966:Substance-Related Disorders / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D003042:Cocaine
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