, Volume 182, Issue 1, pp 65–74 | Cite as

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

Original Investigation



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).


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.


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).


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.


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.


7-OH-DPAT Apomorphine Brain stimulation reward Dopamine Glutamate MK-801 NMDA Nucleus accumbens Self-stimulation Ventral tegmental area 


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Psychiatry, and Centre for NeuroscienceUniversity of AlbertaEdmontonCanada
  2. 2.Department of Psychiatry, 1E7.44 Mackenzie Health Sciences CentreUniversity of AlbertaEdmontonCanada

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