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Reinstatement of cocaine seeking in rats by the pharmacological stressors, corticotropin-releasing factor and yohimbine: role for D1/5 dopamine receptors

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Abstract

Rationale

Two pharmacological stressors commonly used in the study of stress-induced reinstatement of drug seeking are central injections of the stress peptide, corticotropin-releasing factor (CRF), and systemic administration of the α2-adrenoceptor antagonist, yohimbine. Despite the widespread use of these stressors, the neurochemical systems mediating their ability to reinstate cocaine-seeking behaviour have not been fully characterized.

Objective

The present study was designed to characterize the role, specifically, of dopamine transmission in the reinstating effects of CRF and yohimbine on cocaine seeking.

Methods

Male Long-Evans rats were trained to self-administer cocaine (0.23 mg/kg/infusion) for 8–10 days. Subsequently, responding for drug was extinguished, and tests for CRF- (0.5 μg; i.c.v.) and yohimbine-induced (1.25 mg/kg; i.p.) reinstatement were conducted following pretreatment with the dopamine D1/5 receptor antagonists, SCH23390 (0.05, 0.1 mg/kg; i.p.) and/or SCH31966 (0.2 mg/kg; i.p.), and the D2/3 receptor antagonist, raclopride (0.25, 0.5 mg/kg; i.p.).

Results

Pretreatment with SCH23390, but not raclopride, blocked CRF-induced reinstatement of cocaine seeking. Pretreatment with SCH23390 and SCH31966, but not raclopride, blocked yohimbine-induced reinstatement of cocaine seeking.

Conclusions

These findings demonstrate that transmission at D1/5, but not D2/3, receptors mediates the reinstatement of cocaine seeking induced by CRF and yohimbine.

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Abbreviations

5-HT:

Serotonin

ANOVA:

Analysis of variance

CRF:

Corticotropin-releasing factor

FR:

Fixed ratio

i.c.v.:

Intracerebroventricular

i.p.:

Intraperitoneal

i.v.:

Intravenous

mPFC:

Medial prefrontal cortex

PFC:

Prefrontal cortex

SA:

Self-administration

VEH:

Vehicle

VTA:

Ventral tegmental area

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Acknowledgements

This research was supported by a grant from NSERC to S. Erb, and NSERC Canadian Graduate Scholarships to Z.J. Brown and D.A. Kupferschmidt.

Statement of conflicts of interest

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Psychology, Centre for the Neurobiology of Stress, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, M1C 1A4, Canada

    Z. J. Brown, D. A. Kupferschmidt & Suzanne Erb

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  1. Z. J. Brown
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  2. D. A. Kupferschmidt
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  3. Suzanne Erb
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Corresponding author

Correspondence to Suzanne Erb.

Additional information

Z. J. Brown and D. A. Kupferschmidt contributed equally to this work.

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Brown, Z.J., Kupferschmidt, D.A. & Erb, S. Reinstatement of cocaine seeking in rats by the pharmacological stressors, corticotropin-releasing factor and yohimbine: role for D1/5 dopamine receptors. Psychopharmacology 224, 431–440 (2012). https://doi.org/10.1007/s00213-012-2772-3

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