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| Molecular mechanisms of drug addiction |
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| Author(s): Nestler EJ |
| Source: NEUROPHARMACOLOGY Volume: 47 Pages: 24-32 Supplement: Suppl. S Published: 2004 |
| Times Cited: 152 References: 61 |
| Abstract: Regulation of gene expression is one mechanism by which drugs of abuse can induce relatively long-lasting changes in the brain to cause a state of addiction. Here, we focus on two transcription factors, CREB (cAMP response element binding protein) and DeltaFosB, which contribute to drug-induced changes in gene expression. Both are activated in the nucleus accumbens, a major brain reward region, but mediate different aspects of the addicted state. CREB mediates a form of tolerance and dependence, which dampens an individual's sensitivity to subsequent drug exposure and contributes to a negative emotional state during early phases of withdrawal. In contrast, DeltaFosB mediates a state of relatively prolonged sensitization to drug exposure and may contribute to the increased drive and motivation for drug, which is a core symptom of addictive disorders. A major goal of current research is to identify the many target genes through which CREB and DeltaFosB mediate these behavioral states. In addition, future work needs to understand how CREB and DeltaFosB, acting in concert with numerous other drug-induced molecular changes in nucleus accumbens and many other brain regions, interact with one another to produce the complex behavioral phenotype that defines addiction. (C) 2004 Elsevier Ltd. All rights reserved.. |
| Document Type: Article |
| Language: English |
| Reprint Address: Nestler, EJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA |
Addresses:
1. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA
2. Univ Texas, SW Med Ctr, Ctr Basic Neurosci, Dallas, TX 75390 USA |
| Publisher: PERGAMON-ELSEVIER SCIENCE LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND |
| Subject Category: Neurosciences; Pharmacology & Pharmacy |
| IDS Number: 866TV |
| ISSN: 0028-3908 |
| DOI: 10.1016/j.neuropharm.2004.06.031 |
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