Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: a role in stress-induced relapse to drug seeking.
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.
Wang
Bin
B
Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
Shaham
Yavin
Y
Zitzman
Dawnya
D
Azari
Soraya
S
Wise
Roy A
RA
You
Zhi-Bing
ZB
D000818:Animals; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D051381:Rats; D020318:Rats, Long-Evans; D012008:Recurrence; D013312:Stress, Physiological / Q000150:complications*; D017557:Ventral Tegmental Area / Q000378:metabolism*
D018698:Glutamic Acid; D003346:Corticotropin-Releasing Hormone; D004298:Dopamine