Effects of corticotropin-releasing hormone receptor antagonists on cocaine-induced dopamine overflow in the medial prefrontal cortex and nucleus accumbens of rats.
Recent evidence suggests an important role for corticotropin-releasing hormone (CRH) and CRH receptors in cocaine reinforcement. CRH receptor antagonists reduce cocaine self-administration and attenuate the reinstatement of extinguished cocaine-seeking behavior, but little is known about the mechanisms involved. One possible mechanism for these effects may involve the cocaine-induced activation of CRH located in brain regions outside of the hypothalamus. CRH has been shown to increase dopaminergic transmission in regions relevant for cocaine reinforcement, such as the medial prefrontal cortex and the nucleus accumbens. Here, we report that CP-154,526, a CRH1-receptor antagonist, actually enhances cocaine-induced increases in dopamine overflow in the medial prefrontal cortex, measured using in vivo microdialysis. In contrast, the receptor antagonist did not alter cocaine-induced increases in dopamine in most of the nucleus accumbens, except for the most rostral part. These data suggest a surprising role for prefrontal cortex dopamine in the ability of CRH-receptor antagonists to attenuate cocaine seeking in rats.
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Olga V
OV
Gurkovskaya
Vitaly
V
Palamarchouk
Gennady
G
Smagin
Nick E
NE
Goeders
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*
C101628:CP 154526; D018765:Dopamine Uptake Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine; D004298:Dopamine