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A role for corticotropin-releasing factor, but not corticosterone, in acute food-deprivation-induced reinstatement of heroin seeking in rats

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Abstract

Rationale

Acute 1-day food deprivation reinstates heroin seeking in rats via a leptin-dependent mechanism. However, leptin has no effect on footshock- or heroin-priming-induced reinstatement of drug seeking. These data may indicate that the neuronal systems underlying food-deprivation-induced reinstatement are dissociable from those involved in reinstatement induced by footshock stress.

Objectives

We used the reinstatement procedure to examine the roles of the adrenal stress hormone, corticosterone, and brain corticotropin-releasing factor (CRF) in acute food-deprivation-induced reinstatement of extinguished heroin seeking in rats.

Materials and methods

The rats were trained to press a lever for heroin (0.05−0.1 mg/kg/infusion, i.v.) for 10 days. Experiment 1: After heroin self-administration training, the rats were divided into two groups, which received either bilateral adrenalectomy surgery or sham surgery. Next, the rats were given 7–10 days of extinction training (during which lever presses were not reinforced with heroin). The rats were subsequently tested for reinstatement after acute (21 h) food deprivation. Experiment 2: After heroin self-administration and extinction training, the rats were tested for reinstatement induced by acute food deprivation. Before the test session, the rats were given intracerebroventricular injections of the CRF receptor antagonist α-helical CRF (0, 3, or 10 μg/rat).

Results

Adrenalectomy had no effect on the extinction behavior or acute food-deprivation-induced reinstatement of heroin seeking. The CRF receptor antagonist, α-helical CRF, dose-dependently blocked food-deprivation-induced reinstatement.

Conclusions

The present data suggest that, as demonstrated for footshock-induced reinstatement of drug seeking, brain CRF, but not corticosterone, plays a critical role in acute food-deprivation-induced reinstatement of heroin seeking.

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Acknowledgements

Experiment 1 was supported by funds of the intramural program of NIDA/NIH (PI: Yavin Shaham). Experiment 2 was supported by grants from the Canada Research Chair Program and Canada Foundation for Innovation (PI, Uri Shalev). We thank Dr. Michael H. Baumann of the Medication Discovery Research Branch, IRP/NIDA/NIH for his help with plasma corticosterone determination and Dr. Yavin Shaham for helpful comments on a previous version of this manuscript.

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Authors and Affiliations

  1. Department of Psychology, Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada

    Uri Shalev, Peter S. Finnie, Tammie Quinn, Stephanie Tobin & Priti Wahi

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  1. Uri Shalev
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  2. Peter S. Finnie
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Correspondence to Uri Shalev.

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Shalev, U., Finnie, P.S., Quinn, T. et al. A role for corticotropin-releasing factor, but not corticosterone, in acute food-deprivation-induced reinstatement of heroin seeking in rats. Psychopharmacology 187, 376–384 (2006). https://doi.org/10.1007/s00213-006-0427-y

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