Molecular neurobiology of addiction.
Addiction can be viewed as a form of drug-induced neural plasticity. One of the best established molecular mechanisms of addiction is the upregulation of the cAMP second messenger pathway, which occurs in many neuronal cell types in response to chronic administration of opiates or other drugs of abuse. This upregulation and the resulting activation of the transcription factor CREB appear to mediate aspects of tolerance and dependence. In contrast, induction of another transcription factor, termed delta FosB, exerts the opposite effect and may contribute to sensitized responses to drug exposure. Knowledge of these mechanisms could lead to more effective treatments for addictive disorders.
Nestler
E J
EJ
Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9070, USA. eric.nestler@utsouthwestern.edu
D000208:Acute Disease; D000222:Adaptation, Physiological / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002908:Chronic Disease; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000235:genetics; D000431:Ethanol / Q000009:adverse effects; D006801:Humans; D008125:Locus Coeruleus / Q000187:drug effects; D008967:Molecular Biology / Q000379:methods; D009294:Narcotics / Q000009:adverse effects; D009473:Neuronal Plasticity / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000235:genetics; D015290:Second Messenger Systems / Q000187:drug effects / Q000235:genetics; D019966:Substance-Related Disorders / Q000235:genetics*; D015854:Up-Regulation
D017362:Cyclic AMP Response Element-Binding Protein; D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D000242:Cyclic AMP