title: A multistep general theory of transition to addiction.
abstract: BACKGROUND
  Several theories propose alternative explanations for drug addiction.
  
  
  OBJECTIVE
  We propose a general theory of transition to addiction that synthesizes knowledge generated in the field of addiction into a unitary explanatory frame.
  Transition to addiction results from a sequential three-step interaction between: (1) individual vulnerability; (2) degree/amount of drug exposure. The first step, sporadic recreational drug use is a learning process mediated by overactivation of neurobiological substrates of natural rewards that allows most individuals to perceive drugs as highly rewarding stimuli. The second, intensified, sustained, escalated drug use occurs in some vulnerable individuals who have a hyperactive dopaminergic system and impaired prefrontal cortex function. Sustained and prolonged drug use induces incentive sensitization and an allostatic state that makes drugs strongly wanted and needed. Habit formation can also contribute to stabilizing sustained drug use. The last step, loss of control of drug intake and full addiction, is due to a second vulnerable phenotype. This loss-of-control-prone phenotype is triggered by long-term drug exposure and characterized by long-lasting loss of synaptic plasticity in reward areas in the brain that induce a form of behavioral crystallization resulting in loss of control of drug intake. Because of behavioral crystallization, drugs are now not only wanted and needed but also pathologically mourned when absent.
  
  
  CONCLUSIONS
  This general theory demonstrates that drug addiction is a true psychiatric disease caused by a three-step interaction between vulnerable individuals and amount/duration of drug exposure.
authors: Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, INSERM, 146 rue Léo Saignat, Bordeaux, 33076, France, pier-vincenzo.piazza@inserm.fr.
authors: Pier Vincenzo
authors: PV
authors: Piazza
authors: Véronique
authors: V
authors: Deroche-Gamonet
mesh_terms: D016739:Behavior, Addictive; D004361:Drug Tolerance; D058999:Drug-Seeking Behavior; D006801:Humans; D008960:Models, Psychological; D012201:Reward; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders / Q000209:etiology* / Q000523:psychology*
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