Facilitation of brain stimulation reward by MK-801 (dizocilpine) may be independent of D2-like dopamine receptor stimulation in rats
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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.
Keywords7-OH-DPAT Apomorphine Brain stimulation reward Dopamine Glutamate MK-801 NMDA Nucleus accumbens Self-stimulation Ventral tegmental area
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