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Acamprosate attenuates cocaine- and cue-induced reinstatement of cocaine-seeking behavior in rats

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Abstract

Rationale

Acamprosate (calcium acetylhomotaurinate) is a glutamatergic neuromodulator used for the treatment of alcoholism, but its potential efficacy in the treatment of psychostimulant addiction has not been explored.

Objectives

The purpose of this study was to assess the effects of acamprosate on cocaine-stimulated locomotor activity, cocaine self-administration, and cue- and cocaine-induced reinstatement of cocaine-seeking behavior.

Materials and methods

All experiments utilized once-daily treatment for 5 consecutive days. First, the effects of saline or acamprosate (100, 300, or 500 mg/kg intraperitoneally) on body weight were examined. On the last day of treatment, locomotor activity was assessed before and after drug treatment, after which all animals received an acute challenge of cocaine (10 mg/kg). Next, a separate group of rats were trained to intravenously (IV) self-administer cocaine (0.6 mg/kg per infusion), subjected to extinction procedures, and then tested for effects of acamprosate on cue- or cocaine-induced reinstatement. A third group of rats was trained to self-administer cocaine as described above and were treated with saline or acamprosate before daily IV self-administration sessions.

Results

Repeated administration of 500 mg/kg acamprosate but not lower doses produced reductions in both body weight and spontaneous locomotor activity, and thus this dose was not tested further. Acamprosate at 300 mg/kg but not 100 mg/kg attenuated both cocaine- and cue-induced reinstatement without altering baseline patterns of cocaine self-administration or cocaine-stimulated hyperlocomotion.

Conclusions

Acamprosate attenuates both drug- and cue-induced reinstatement of cocaine-seeking behavior, suggesting that this compound may serve as a potential treatment for preventing relapse in cocaine-addicted humans.

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Acknowledgments

This work was supported by the Neurobiology of Addiction Research Center (DA015369) and funds provided by the State of California for medical research on alcohol and substance abuse through the University of California at San Francisco. The authors wish to thank Shannon Ghee and Brian Wheeler for technical assistance.

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Authors and Affiliations

  1. Ernest Gallo Clinic and Research Center, Department of Neurology, University of California at San Francisco, Emeryville, CA, 94608, USA

    M. Scott Bowers, Billy T. Chen, Jonathan K. Chou, Antonello Bonci & Patricia H. Janak

  2. Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President Street, P.O. Box 250861, Charleston, SC, 29425, USA

    Megan P. H. Osborne, Justin T. Gass, Ronald E. See & M. Foster Olive

  3. Department of Neurosciences, Medical University of South Carolina, Charleston, SC, 29425, USA

    Ronald E. See

  4. Wheeler Center for the Neurobiology of Addiction, University of California at San Francisco, San Francisco, CA, 94143, USA

    Antonello Bonci & Patricia H. Janak

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  1. M. Scott Bowers
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  2. Billy T. Chen
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Correspondence to M. Foster Olive.

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Bowers, M.S., Chen, B.T., Chou, J.K. et al. Acamprosate attenuates cocaine- and cue-induced reinstatement of cocaine-seeking behavior in rats. Psychopharmacology 195, 397–406 (2007). https://doi.org/10.1007/s00213-007-0904-y

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  • DOI: https://doi.org/10.1007/s00213-007-0904-y

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