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The effects of chronic buprenorphine on intake of heroin and cocaine in rats and its effects on nucleus accumbens dopamine levels during self-administration

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Abstract

Rationale

Buprenorphine reduces both heroin and cocaine intake in opioid addicts, but the mechanisms remain unclear.

Objectives

To determine the effects of chronic buprenorphine treatment on intake of heroin and/or cocaine and measure nucleus accumbens (NAc) dopamine (DA) levels during self-administration.

Methods

In experiment 1, plasma levels of buprenorphine were determined in rats with buprenorphine osmotic minipumps (3.0 mg/kg/day) using an ELISA. In experiment 2, rats self-administered (FR1) one dose of heroin [(0.025, 0.05, or 0.1 mg/kg/infusion (inf)] and one dose of cocaine (0.25, 0.5, or 1.0 mg/kg/inf) before and under sham or chronic buprenorphine treatment (1.5 or 3.0 mg/kg/day). In experiment 3, the effect of sham or chronic buprenorphine treatment (3.0) on heroin (0.05 mg/kg/inf) or cocaine (0.5 mg/kg/inf) self-administration under FR5 and progressive ratio (PR) schedules was evaluated. In experiment 4, in vivo microdialysis sampling from the NAc was carried out during heroin (0.05 mg/kg/inf) or cocaine (0.5 mg/kg/inf) self-administration (FR1) under sham or buprenorphine treatment (3.0).

Results

Buprenorphine levels in plasma were stable over time. Buprenorphine treatment had no effect on total heroin intake at any dose or under any schedule, whereas it suppressed cocaine intake at all doses and under all schedules. Buprenorphine enhanced basal levels of DA, attenuated the NAc DA response to heroin, and enhanced the DA response to cocaine. It is interesting to note that buprenorphine increased the latency to respond to drug-associated cues at the start of self-administration sessions.

Conclusions

Chronic buprenorphine reduces cocaine, but not heroin, intake and possibly reduces drug seeking by reducing the salience of the drug-associated cues.

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Acknowledgements

The authors wish to thank Heshmat Rajabi for his assistance with microdialysis and HPLC technical support. This research was supported by an Interdisciplinary Health Research Team (IHRT) grant from the Canadian Institutes of Health Research (CIHR), and operating grants from CIHR and le fonds québécois de la recherche sur la nature et les technologies (FQRNT) to J.S. R.E.S. was supported by a graduate fellowship from the Natural Science and Engineering Council of Canada (NSERC).

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  1. Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, SP 244, 7141 Sherbrooke Street West, Montreal, Quebec, H4B 1R6, Canada

    Robert E. Sorge & Jane Stewart

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  1. Robert E. Sorge
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  2. Jane Stewart
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Correspondence to Jane Stewart.

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Sorge, R.E., Stewart, J. The effects of chronic buprenorphine on intake of heroin and cocaine in rats and its effects on nucleus accumbens dopamine levels during self-administration. Psychopharmacology 188, 28–41 (2006). https://doi.org/10.1007/s00213-006-0485-1

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  • DOI: https://doi.org/10.1007/s00213-006-0485-1

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