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A reliable method to study cue-, priming-, and stress-induced reinstatement of cocaine self-administration in mice

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Abstract

Rationale

Cocaine addiction is a relapsing psychiatric disorder with a high prevalence in developed countries. To date, the reinstatement model has been difficult to implement in mice. The design of an appropriate reinstatement model in mice is required in order to use genetically modified animals with the aim of clarifying the mechanisms involved in cocaine relapse.

Objectives

Our aim was to develop an appropriate model of reinstatement of cocaine-seeking behavior and to investigate the factors that can trigger this reinstatement by using an operant intravenous self-administration procedure in mice. Discrete cues, priming injection of cocaine, and exposure to stress were the stimuli used to reinstate cocaine-seeking behavior.

Material and methods

Mice were trained to acquire intravenous self-administration of cocaine (1 mg/kg per infusion) on a fixed ratio 1 (FR1) schedule of reinforcement. After achieving the acquisition criteria, animals were led to extinguish the operant behavior. Subsequently, under extinction conditions, mice were tested after the administration of a cocaine priming injection (10 mg/kg i.p.), the presentation of a light cue associated with cocaine administration, or the exposure to a stressful situation (0.21 mA electric footshock).

Results

Under our experimental conditions the three stimuli successfully reinstated an extinguished cocaine-seeking behavior. Reexposure to cocaine effects by a priming injection was revealed as the strongest stimulus, capable of reinstating cocaine-seeking behavior.

Conclusions

The effective reinstatement model that we have developed will become a useful tool for future understanding of the neurobiological basis of cocaine addiction and relapse, specifically, with the use of genetically modified mice.

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Abbreviations

i.p.:

intraperitoneally

i.v.:

intravenous

FR:

fixed ratio

CPP:

conditioned place preference

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Acknowledgments

The authors wish to thank S.A. Bura and Dr. B. Rubi for critical reading of the manuscript. This study was supported by grants from Spanish MCYT (SAF2004/0568; SAF2007/60249) and MSC (Plan Nacional sobre Drogodependencias, conv, 2006) to O.V., and (SAF2007-64062) to R.M., and European Communities (Genaddict LSHMCT-2004-005166; Phecomp LSHMCT-2006-037669) to R.M. G.S. was supported by a fellowship from Spanish MCYT associated with the SAF2004/0568 grant. M.F.B. was supported by a postdoctoral fellowship from the Fyssen Foundation.

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Author notes

  1. Guadalupe Soria

    Present address: Department of Cerebral Ischemia and Neurodegeneration, Institut d’Investigacions Biomèdiques de Barcelona (CSIC), IDIBAPS, Rosselló, 161, 6th floor, 08036, Barcelona, Spain

  2. Maria Flavia Barbano

    Present address: Instituto de Investigaciones Biotecnológicas, Universidad de General San Martín, INTI - Colectora Av.General Paz 5445, edificio 24, casilla de correos 30, CP 1650, San Martin, Buenos Aires, Argentina

Authors and Affiliations

  1. Laboratorio de Neurofarmacología, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona. C/Dr. Aiguader 88, 08003, Barcelona, Spain

    Guadalupe Soria, Maria Flavia Barbano & Rafael Maldonado

  2. Grup de Recerca de Neurobiologia del Comportament (GRNC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, C/Doctor Aiguader 88, 08003, Barcelona, Spain

    Olga Valverde

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  1. Guadalupe Soria
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Correspondence to Olga Valverde.

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Soria, G., Barbano, M.F., Maldonado, R. et al. A reliable method to study cue-, priming-, and stress-induced reinstatement of cocaine self-administration in mice. Psychopharmacology 199, 593–603 (2008). https://doi.org/10.1007/s00213-008-1184-x

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  • DOI: https://doi.org/10.1007/s00213-008-1184-x

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