Facilitation of brain stimulation reward by MK-801 (dizocilpine) may be independent of D2-like dopamine receptor stimulation in rats.
BACKGROUND
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 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor blockade and D(2/3) DA receptor stimulation in brain stimulation reward (BSR).


OBJECTIVE
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 mug intra-NAS) reduced reward thresholds while 7-OH-DPAT (0.03 mg kg(-1) s.c. or 5.0 microg 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 D(2/3) 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.
Clements
R L H
RL
Department of Psychiatry, and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, T6G 2B7, Canada.
Greenshaw
A J
AJ
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004292:Dominance, Cerebral / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology; D004347:Drug Interactions; D009042:Motivation; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects*
D015259:Dopamine Agents; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D013764:Tetrahydronaphthalenes; D016291:Dizocilpine Maleate; D001058:Apomorphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin