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Blockade of substantia nigra dopamine D1 receptors reduces intravenous cocaine reward in rats

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Abstract

Rationale

We have recently found that blockade of dopamine D1-type receptors in the ventral tegmental area reduces the rewarding effects of intravenous cocaine; here, we explored the possibility that blockade of D1 receptors in the adjacent substantia nigra (SN)—not usually considered part of reward circuitry—might have similar effects.

Objective

To test the hypothesis that blockade of dopamine D1 receptors in the SN reduces the rewarding effects of cocaine.

Methods

Twenty one rats were prepared with intravenous catheters and with bilateral guide cannulae implanted such that injections could be made directly into the SN or just dorsal to the SN. The rats were trained to self-administer intravenous cocaine (1.0 mg/kg per injection) on a fixed-ratio 1 (FR1) schedule of reinforcement. After stable responding developed, 13 of the animals were tested following pretreatment with bilateral microinjections of SCH 23390 at doses of 0, 1, 2 or 4 μg/0.5 μl into the SN and 8 were tested with injections of 0 μg or 4 μg/0.5 μl into a site 2 mm dorsal to the SN site.

Results

Microinjections of SCH 23390 in the SN significantly increased rates of cocaine self-administration, while injections dorsal to SN had no significant effect on responding.

Conclusions

These data suggest that blockade of dendritically released DA in the SN reduces the rewarding effects of cocaine. These findings complement accumulating evidence that the rewarding effects of cocaine are not restricted to the drug’s ability to elevate dopamine levels in the nucleus accumbens.

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Acknowledgements

This research was supported by a NIDA grant (DA01720) to Roy Wise and by a PSC-CUNY Research Foundation grant to Robert Ranaldi. Part of this work was completed at Concordia University and part of it at Queens College/CUNY. The authors wish to thank Zafiro Koty for her excellent technical assistance.

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Authors and Affiliations

  1. Department of Psychology, Queens College, CUNY, 65-30 Kissena Boulevard, Flushing, NY 11367, USA

    Matthew G. Quinlan, Ruth Sharf, David Y. Lee & Robert Ranaldi

  2. Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA

    Roy A. Wise

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  1. Matthew G. Quinlan
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  2. Ruth Sharf
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  3. David Y. Lee
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  4. Roy A. Wise
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  5. Robert Ranaldi
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Correspondence to Robert Ranaldi.

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Quinlan, M.G., Sharf, R., Lee, D.Y. et al. Blockade of substantia nigra dopamine D1 receptors reduces intravenous cocaine reward in rats. Psychopharmacology 175, 53–59 (2004). https://doi.org/10.1007/s00213-003-1771-9

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  • DOI: https://doi.org/10.1007/s00213-003-1771-9

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