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Facilitation of brain stimulation reward by MK-801 (dizocilpine) may be independent of D2-like dopamine receptor stimulation in rats

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Abstract

Rationale

Dopamine (DA) and glutamate (Glu) interactions in the mesocorticolimbic pathway may regulate motivation and reward and contribute to schizophrenia and drug abuse. We have recently demonstrated synergistic effects of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor blockade and D2/3 DA receptor stimulation in brain stimulation reward (BSR).

Objectives

This study was conducted to explore interactions between DA and Glu systems in BSR using the NMDA receptor antagonist MK-801 and the DA receptor agonists 7-OH-DPAT and apomorphine.

Methods

Systemic effects of these compounds were measured in male Sprague–Dawley rats using rate–frequency threshold analysis of ventral tegmental area (VTA) BSR (n=27). Effects of bilateral applications of MK-801 and 7-OH-DPAT into the nucleus accumbens (NAS) shell subregion were also investigated (n=10).

Results

MK-801 (0.03 or 0.13 mg kg−1 i.p. or 0.66 μg intra-NAS) reduced reward thresholds while 7-OH-DPAT (0.03 mg kg−1 s.c. or 5.0 μg intra-NAS) or apomorphine (0.05 mg kg−1, s.c.) increased this measure. MK-801 combined with apomorphine or with 7-OH-DPAT, systemically or in the NAS shell, induced additive effects.

Conclusions

Lack of interaction between DA agonists and MK-801 in this study contrasts with our previous work showing synergistic reward-decreased effects of AMPA/kainate receptor blockade and D2/3 DA receptor stimulation in the NAS shell, and indicates possible independence of DA and N-methyl-d-aspartate (NMDA) receptor effects in VTA electrical self-stimulation.

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Acknowledgements

This work was funded by the Canadian Institutes of Health Research. We express our thanks to Satyabrata Kar and David J. Hayes for their histology assistance. R.L.H. Clements was the recipient of a postgraduate scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC).

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Authors and Affiliations

  1. Department of Psychiatry, and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, T6G 2B7, Canada

    R. L. H. Clements & A. J. Greenshaw

  2. Department of Psychiatry, 1E7.44 Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Alberta, T6G 2R7, Canada

    A. J. Greenshaw

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  1. R. L. H. Clements
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Correspondence to A. J. Greenshaw.

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Clements, R.L.H., Greenshaw, A.J. Facilitation of brain stimulation reward by MK-801 (dizocilpine) may be independent of D2-like dopamine receptor stimulation in rats. Psychopharmacology 182, 65–74 (2005). https://doi.org/10.1007/s00213-005-0039-y

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  • DOI: https://doi.org/10.1007/s00213-005-0039-y

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