Original investigation


, Volume 185, Issue 1, pp 19-28

First online:

Region-specific effects of brain corticotropin-releasing factor receptor type 1 blockade on footshock-stress- or drug-priming-induced reinstatement of morphine conditioned place preference in rats

  • Jishi WangAffiliated withDepartment of Pharmacology, The Affiliated Hospital of Guiyang Medical CollegeDepartment of Pharmacology, New York Medical College
  • , Qin FangAffiliated withDepartment of Pharmacology, The Affiliated Hospital of Guiyang Medical College
  • , Zhonghua LiuAffiliated withBehavioral Neuroscience Branch, National Institute on Drug Abuse, IRP/NIDA/NIH/DHHS
  • , Lin LuAffiliated withNational Laboratory of Medical Neurobiology, Shanghai Medical School Fudan UniversityNational Institute on Drug Dependence, Peking UniversityBehavioral Neuroscience Branch, National Institute on Drug Abuse, IRP/NIDA/NIH/DHHS Email author 

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Systemic injections of the selective corticotropin-releasing factor 1 (CRF1) receptor antagonist CP-154,526 attenuate footshock-stress-induced reinstatement of heroin and cocaine seeking and morphine conditioned place preference (CPP). Intracranial injections of the nonselective CRF receptor antagonist d-Phe-CRF into the bed nucleus of the stria terminalis (BNST), but not the amygdala, attenuate footshock-induced reinstatement of cocaine seeking. However, the brain sites involved in the effect of CP-154,526 on footshock-induced reinstatement of opiate seeking are unknown.


We used a CPP version of the reinstatement model to examine the role of CRF1 receptors in the BNST, amygdala, and nucleus accumbens (NAc) in footshock- or drug-priming-induced reinstatement of extinguished morphine CPP.


Rats acquired morphine CPP over a period of 8 days during which they were given four morphine (10 mg/kg s.c.) and four saline injections and were subsequently confined to distinct chambers for 50 min. Subsequently, the morphine CPP was extinguished in 14 daily sessions during which rats were given saline injections and given access to both the saline- and morphine-paired chambers. The rats were then tested for reinstatement of morphine CPP induced by priming injections of morphine (0 or 3.0 mg/kg s.c.) or by exposure to intermittent footshock (15 min, 0.5 mA). Prior to the test sessions, the rats were given intracranial injections of CP-154,526 (1.0 μg) or vehicle into the BNST, amygdala, or NAc.


CP-154,526 injections into the BNST, but not the amygdala or NAc, attenuated footshock-stress-induced reinstatement of morphine CPP. In contrast, CP-154,526 injections into the amygdala or NAc, but not the BNST, attenuated morphine-priming-induced reinstatement of morphine CPP.


The present results demonstrate dissociable roles of CRF1 receptors in the BNST, amygdala, and NAc in footshock-stress- vs morphine-priming-induced reinstatement of drug CPP.


Amygdala Bed nucleus of the stria terminalis Corticotropin-releasing factor Conditioned place preference Nucleus accumbens Opiate Reinstatement Relapse