Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function.
Psychopharmacology. 2005-02-25; 180(3): 473-490
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1. Psychopharmacology (Berl). 2005 Jul;180(3):473-90. Epub 2005 Feb 25.
Transition to drug addiction: a negative reinforcement model based on an
allostatic decrease in reward function.
Ahmed SH(1), Koob GF.
(1)Laboratoire de Neuropsychobiologie des Désadaptations, University
Victor-Segalen Bordeaux2, CNRS-UMR 5541, 33076, Bordeaux, France.
Psychopharmacology (Berl). 2012 Mar;220(1):247.
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
overactivation 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, 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.
PMID: 15731896 [Indexed for MEDLINE]