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The Journal of Neuroscience, June 1, 2005, 25(22):5389-5396; doi:10.1523/JNEUROSCI.0955-05.2005

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Behavioral/Systems/Cognitive
Cocaine Experience Establishes Control of Midbrain Glutamate and Dopamine by Corticotropin-Releasing Factor: A Role in Stress-Induced Relapse to Drug Seeking

Bin Wang, Yavin Shaham, Dawnya Zitzman, Soraya Azari, Roy A. Wise, and Zhi-Bing You

Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224

Footshock stress can reinstate cocaine-seeking behavior through a central action of the stress-associated neurohormone corticotropin-releasing factor (CRF). Here we report (1) that footshock stress releases CRF in the ventral tegmental area (VTA) of the rat brain, (2) that, in cocaine-experienced but not in cocaine-naive rats, this CRF acquires control over local glutamate release, (3) that CRF-induced glutamate release activates the mesocorticolimbic dopamine system, and (4) that, through this circuitry, footshock stress triggers relapse to drug seeking in cocaine-experienced animals. Thus, a long-lasting cocaine-induced neuroadaptation, presumably at the level of glutamate terminals in the VTA, appears to play an important role in stress-induced relapse to drug use. Similar neuroadaptations may be important for the comorbidity between addiction and other stress-related psychiatric disorders.

Key words: stress; addiction; relapse; ventral tegmental area; corticotropin-releasing factor; cocaine

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Received March 10, 2005; revised April 27, 2005; accepted April 27, 2005.

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				M. J. Wanat, F. W. Hopf, G. D. Stuber, P. E. M. Phillips, and A. Bonci Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of Ih J. Physiol., April 15, 2008; 586(8): 2157 - 2170. [Abstract] [Full Text] [PDF]

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				Z.-B. You, B. Wang, D. Zitzman, S. Azari, and R. A. Wise A Role for Conditioned Ventral Tegmental Glutamate Release in Cocaine Seeking J. Neurosci., September 26, 2007; 27(39): 10546 - 10555. [Abstract] [Full Text] [PDF]

				B. Boutrel, P. J. Kenny, S. E. Specio, R. Martin-Fardon, A. Markou, G. F. Koob, and L. de Lecea Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior PNAS, December 27, 2005; 102(52): 19168 - 19173. [Abstract] [Full Text] [PDF]

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