drug addiction: pathways to the disease and pathophysiological perspectives

REVIEW Drug addiction: Pathways to the disease and pathophysiological perspectives ☆ Michel Le Moal a , ⁎ , George F. Koob b a Laboratoire Physiopathologie du Comportement — Inserm U.588, Institut François Magendie, 146 rue Léo Saignat, 33077 Bordeaux Cedex, France b Department of Neuropharmacologie – The Scripps Research Institute – La Jolla, California, USA Received 16 May 2006; received in revised form 28 August 2006; accepted 24 October 2006 Abstract Drug addicti on is a med ic al condition, a chr onic relapsing disease . As in ot her domains of experimental medicine, appropriate experimental investigations are needed in order to better understand the disease. However, to understand the diverse facets of drug effects and of the underl yi ng pat hop hy siolo gy it is neces sa ry to kee p in mind the compl exi ty of the psychop athologi cal proces ses. The main symptoms that characterize addiction correspond to exp ression s of dysf unction s wit hin spec ific circ uits and reg ion s. P athw ays to addiction are numero us and comorb idi ty and in the real world pol y-d rug use are common. Some of these aspects will be examined as well as the role of life events and stress. Theoretical considerations will be proposed [see also: Koob, G.F., & Le Moal, M.. 2005a. Neurobiology of Addiction. Elsevier. 570 pp] to account for the stages of the disease from impulse control disorder to compulsive di sor ders, for aff ect ive dynami cs and for the rel ati ons between the symptoms and pathophysiology. © 2006 Elsevier B.V. and ECNP. All rights reserved. KEYWORDS Drug addiction; Definition physiopathology 1. The problem of definition Historicall y , the last stage s of a drug misuse escalatio n was defined as a state of dependence, an arbitary term used to denote the presence of an acquired abnormal state wherein the regular administration of adequate amount of a drug has, through previous prolonged use, become requisite to physi ologic equilibrium. Sin ce it is not yet possible to diagnose physical dependence objectively without withhold- ing drugs, the sine qua non of physical dependence remains the demonstration of a phy sical abstinence syndrome Q (Himmelsbach, 1943). This authoritative defin ition evolved into the def ini tio n of phy sical dep endenc e, an int ens e physi cal disturbance when drug usage was discontinue d. Then, when no physical signs were observed, obvious other aspects of the process were considered, in particular the behavioral and psychic symptoms, resulting in the definition of psychic dependence, a condition in which a drug produces a feeling of satisfaction and a psychic drive that require periodic or continuous administration of the drug to produce pleasure or to avoid discomfort… Q (Eddy et al., 1965). More recent definitions resemble a combination of Himmelsbach's phy sical and psy chi c dep end enc e with emp hasis on the psychic and motivational aspects of withdrawal: Addiction comes fro m the Latin verb addicere Q , to give or bind a ☆ Michel Le Moal is the recipient of the 2005 ECNP Neuropsycho- pharmacology Award in Basic Science. This paper has been written to mark this occasion. ⁎ Corre spo ndi ngauthor. Tel.: +335 57 57 36 61;fax:+33 5 57 57 36 69. E-mail address: [email protected] (M. Le Moal). 0924-977X /$ - see front matter © 2006 Elsevier B.V . and ECNP. All rights reserved. doi:10.1016/j.euroneuro.2006.10.006 www.elsevier.com/locate/euroneuro European Neuropsychopharmacology (2007) 17, 377–393

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