Abstract

The concept of incubation of craving in humans was first noted over 25 years ago in cocaine addicts who experienced increased drug craving and drug seeking in response to drug cues that persisted even after long periods of abstinence ( 1 Gawin F.H. Kleber H.D. Abstinence symptomatology and psychiatric diagnosis in cocaine abusers: Clinical observations. Arch Gen Psychiatry. 1986; 43: 107-113 Crossref PubMed Scopus (954) Google Scholar ). This phenomenon has since been observed using the extinction/reinstatement paradigm in rodents. Animals have shown time-dependent increases in drug seeking after withdrawal from cocaine ( 2 Grimm J.W. Hope B.T. Wise R.A. Shaham Y. Incubation of cocaine craving after withdrawal. Nature. 2001; 412: 141-142 Crossref PubMed Scopus (732) Google Scholar ), alcohol ( 3 Bienowski P. Rogowski A. Korkosz A. Mierzejewski P. Radwanska K. Kaczmarek L. et al. Time-dependent changes in alcohol seeking behaviour during abstinence. Eur Neuropsychopharmacol. 2003; 14: 355-360 Abstract Full Text Full Text PDF Scopus (77) Google Scholar ), heroin ( 4 Shalev U. Morales M. Hope B. Yap J. Shaham Y. Time-dependent changes in extinction behavior and stress-induced reinstatement of drug seeking following withdrawal from heroin in rats. Psychopharmacology (Berl). 2001; 156: 98-107 Crossref PubMed Scopus (225) Google Scholar ), and methamphetamine ( 5 Shepard J.D. Bossert J.M. Liu S.Y. Shaham Y. The anxiogenic drug yohimbine reinstates methamphetamine seeking in a rat model of drug relapse. Biol Psychiatry. 2004; 55: 1082-1089 Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar ). Dovetailing this work, Bedi et al. ( 6 Bedi G. Preston K.L. Epstein D.H. Heishman S.J. Marrone G.F. Shaham Y. de Wit H. Incubation of cue-induced cigarette craving during abstinence in human smokers. Biol Psychiatry. 2011; 69: 708-711 Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar ) found that cue-induced craving in abstinent human smokers increases with time, even as baseline levels of craving and withdrawal decrease. Taken together, this evidence has clear implications for treatment and relapse prevention. However, mechanisms underlying incubation of craving are not well understood, and it is unclear whether drug cues alone precipitate incubation of craving and relapse or whether another confounding factor, such as stress, may be the causal agent. Stress is known to be a significant risk factor that predisposes individuals to develop substance use disorders and puts recovering addicts at risk for relapse ( 7 Sinha R. Chronic stress, drug use and vulnerability to addiction. Ann N Y Acad Sci. 2008; 1141: 105-130 Crossref PubMed Scopus (1070) Google Scholar ). By looking at the role of stress using parallel animal and human models, we can perhaps gain a new perspective on the issue of incubation of craving.

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