R L H Clements1, A J Greenshaw. 1. Department of Psychiatry, and Centre for Neuroscience, University of Alberta, Edmonton, Alberta, T6G 2B7, Canada.
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 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). 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 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.
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 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). 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 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.
Authors: Jérôme Maheux; Michel St-Hilaire; David Voyer; Emanuele Tirotta; Emiliana Borrelli; Claude Rouillard; Pierre-Paul Rompré; Daniel Lévesque Journal: Front Pharmacol Date: 2012-08-14 Impact factor: 5.810