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Measuring the incentive value of escalating doses of heroin in heroin-dependent Fischer rats during acute spontaneous withdrawal

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Abstract

Rationale/objectives

Although continued heroin use and relapse are thought to be motivated, in part, by the positive incentive-motivational value attributed to heroin, little is understood about heroin’s incentive value during the relapse-prone state of withdrawal. This study uses place preference to measure the incentive value attributed to escalating-dose heroin in the context of heroin dependence.

Methods

Male Fischer rats were exposed chronically to escalating doses of heroin in the homecage and during place preference conditioning sessions. Conditioned preference for the context paired with escalating-dose heroin was tested after homecage exposure was discontinued and rats entered acute spontaneous withdrawal. Individuals’ behavioral and locomotor responses to heroin and somatic withdrawal signs were recorded.

Results

Conditioned preference for the heroin-paired context was strong in rats that received chronic homecage exposure to escalating-dose heroin and were tested in acute withdrawal. Behavioral responses to heroin (e.g., stereotypy) varied widely across individuals, with rats that expressed stronger heroin preference also expressing stronger behavioral activation in response to heroin. Individual differences in preference were also related to locomotor responses to heroin but not to overt somatic withdrawal signs.

Conclusions

Escalating doses of heroin evoked place preference in rats, suggesting that positive incentive-motivational value is attributed to this clinically relevant pattern of drug exposure. This study offers an improved preclinical model for studying dependence and withdrawal and provides insight into individual vulnerabilities to addiction-like behavior.

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Acknowledgements

This research was supported by NIH-NIDA P60-DA-05130-24 to M.J.K., and the Dorothea Dix Postdoctoral Fellowship and NIH-NIDA 1F32DA030831-01 to K.M.S. Diacetylmorphine hydrochloride was generously provided by NIH-NIDA Division of Drug Supply and Analytical Services. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health. The authors have no conflicts of interest, financial or otherwise, pertaining to any aspect of the work reported in this manuscript. All experiments described herein comply with the current laws of the country in which they were performed.

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  1. Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA

    Katharine M. Seip, Brian Reed, Ann Ho & Mary Jeanne Kreek

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  1. Katharine M. Seip
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Correspondence to Katharine M. Seip.

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Seip, K.M., Reed, B., Ho, A. et al. Measuring the incentive value of escalating doses of heroin in heroin-dependent Fischer rats during acute spontaneous withdrawal. Psychopharmacology 219, 59–72 (2012). https://doi.org/10.1007/s00213-011-2380-7

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