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Cocaine-induced reinstatement in rats: evidence for a critical role of cocaine stimulus properties

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Abstract

Rationale

The exact behavioral nature of drug-induced reinstatement of drug seeking is still debated. As an incentive, the drug can have general facilitatory influences on appetitive behaviors. As an interoceptive stimulus, the drug can acquire discriminative properties and control behavior.

Objective

This study assessed the relative contribution of the incentive versus discriminative properties of cocaine in food-seeking reinstatement.

Methods

In Experiment 1, eight groups of rats were trained to press a lever for food pellets and experienced cocaine (0, 5, 10, or 15 mg/kg; i.p.), either during the operant conditioning sessions or 4 h after, in another environment without food access. In Experiment 2, to dissociate the role of the operant response per se from the consummatory response, two groups of rats experienced food consumption under cocaine (10 mg/kg; i.p.) either during operant conditioning sessions or during alternate sessions of free access to the food. Then, for both experiments, food pellets were withheld and cocaine injections ceased (extinction). The reinstating effects of noncontingent cocaine (10 mg/kg; i.p.) and food pellet delivery were assessed. Locomotor activity was recorded to probe expression of behavioral sensitization.

Results

Cocaine reinstated lever pressing only in rats having previously performed the operant responses under cocaine. In contrast, food pellet delivery reinstated lever pressing independently of rats’ history with cocaine. Locomotor sensitization was evidenced for all cocaine-pre-exposed rats, dissociating sensitization from reinstatement.

Conclusions

When present during operant conditioning, the stimulus “cocaine” acquires conditioned properties which can then promote reinstatement of the extinguished behavior.

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Acknowledgements

We are grateful to Anne Fayoux and Stephane Lelgouach for animal care, Pierre Gonzalez for technical support, Caroline Vouillac for logistic assistance, and Marie-Hélène Bruyères for administrative assistance. We also thank Dr. Kelly Clemens for her constructive comments on an earlier version of the manuscript.

Conflict of interest statement

The authors declare no financial conflict of interest. The present work was supported by the Centre National de la Recherche Scientifique, University of Bordeaux 1 and 2, the Mission Interministérielle de Lutte contre la Drogue & la Toxicomanie, and the “Conseil Régional d’Aquitaine.” Ronald Keiflin is supported by a doctoral fellowship from the French Ministry of Research and Technology.

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Authors and Affiliations

  1. University of Bordeaux 2; University of Bordeaux 1; CNRS; UMR 5227, Movement–Adaptation–Cognition; Team “neuropsychopharmacology of addiction”, 146 rue Leo Saignat, 33076, Bordeaux, France

    Ronald Keiflin, Elsa Isingrini & Martine Cador

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  1. Ronald Keiflin
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Correspondence to Ronald Keiflin.

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Keiflin, R., Isingrini, E. & Cador, M. Cocaine-induced reinstatement in rats: evidence for a critical role of cocaine stimulus properties. Psychopharmacology 197, 649–660 (2008). https://doi.org/10.1007/s00213-008-1083-1

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