Article abstract
Nature Neuroscience 10, 1029 - 1037 (2007)
Published online: 8 July 2007 | doi:10.1038/nn1929
Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse
Danielle L Graham1, Scott Edwards1, Ryan K Bachtell1, Ralph J DiLeone2, Maribel Rios3 & David W Self1
Abstract
A single exposure to cocaine rapidly induces the brief activation of several immediate early genes, but the role of such short-term regulation in the enduring consequences of cocaine use is poorly understood. We found that 4 h of intravenous cocaine self-administration in rats induced a transient increase in brain-derived neurotrophic factor (BDNF) and activation of TrkB-mediated signaling in the nucleus accumbens (NAc). Augmenting this dynamic regulation with five daily NAc BDNF infusions caused enduring increases in cocaine self-administration, and facilitated relapse to cocaine seeking in withdrawal. In contrast, neutralizing endogenous BDNF regulation with intra-NAc infusions of antibody to BDNF subsequently reduced cocaine self-administration and attenuated relapse. Using localized inducible BDNF knockout in mice, we found that BDNF originating from NAc neurons was necessary for maintaining increased cocaine self-administration. These findings suggest that dynamic induction and release of BDNF from NAc neurons during cocaine use promotes the development and persistence of addictive behavior.
- Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
- Department of Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center, 34 Park Street, New Haven, Connecticut 06508, USA.
- Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA.
Correspondence to: David W Self1 e-mail: david.self@utsouthwestern.edu.
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