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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

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Abstract

Rationale

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.

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgements

This work was supported in part by the grant from the Public Health Ministry of China, the National Basic Research Program of China (No. 20003CB 515400 to Dr. Lin Lu), and the National Natural Science Foundation of China (No. 30570576 to Dr. Lin Lu). We thank Dr. Yavin Shaham and Dr. Udi Ghitza for the helpful comments.

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Authors and Affiliations

  1. Department of Pharmacology, The Affiliated Hospital of Guiyang Medical College, Guiyang, 550004, China

    Jishi Wang & Qin Fang

  2. Department of Pharmacology, New York Medical College, Valharla, NY, 10595, USA

    Jishi Wang

  3. Behavioral Neuroscience Branch, National Institute on Drug Abuse, IRP/NIDA/NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA

    Zhonghua Liu & Lin Lu

  4. National Laboratory of Medical Neurobiology, Shanghai Medical School Fudan University, Shanghai, 200032, China

    Lin Lu

  5. National Institute on Drug Dependence, Peking University, Beijing, 100083, China

    Lin Lu

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  1. Jishi Wang
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  2. Qin Fang
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  4. Lin Lu
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Correspondence to Lin Lu.

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The authors J. Wang and Q. Fang contributed equally to this work.

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Wang, J., Fang, Q., Liu, Z. et al. 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. Psychopharmacology 185, 19–28 (2006). https://doi.org/10.1007/s00213-005-0262-6

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