NMDA or AMPA/kainate receptor blockade prevents acquisition of conditioned place preference induced by D2/3 dopamine receptor stimulation in rats
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Recent experiments from this laboratory demonstrated synergistic effects of AMPA/kainate receptor blockade and D2/3 dopamine (DA) receptor stimulation on brain stimulation reward and locomotor activity.
Using place conditioning, this study explored further the interaction between DA and glutamate (Glu) using the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801, the AMPA/kainate receptor antagonist NBQX, and the D2/3 DA receptor agonist 7-OH-DPAT.
Effects of these compounds, alone and combined, were measured in male Sprague–Dawley rats using an unbiased two-compartment place conditioning procedure.
7-OH-DPAT (0.03–5.0 mg kg−1, s.c.) administered immediately prior to conditioning was ineffective; when administered 15 min prior to conditioning, only the highest dose (5.0 mg kg−1, s.c.) induced conditioned place preference (CPP). Acquisition of 7-OH-DPAT-induced CPP was blocked by MK-801 (0.06 or 0.13 mg kg−1, i.p.) or NBQX (0.5 μg) microinjected into the nucleus accumbens (NAS) shell subregion. Intra-NAS shell administration of 7-OH-DPAT (5.0 μg) or NBQX (0.5 μg), alone or combined, failed to induce place conditioning, and this lack of effect was not due to state dependency. Administration of MK-801 or 7-OH-DPAT (5.0 mg kg−1) during the conditioning phase acutely increased horizontal activity, but neither compound, alone or combined, induced conditioned locomotor effects.
Acquisition of place conditioning induced by systemic administration of 7-OH-DPAT is blocked by systemic NMDA receptor antagonism by MK-801 or by the AMPA/kainate receptor antagonist NBQX microinjected into the NAS shell subregion.
Keywords7-OH-DPAT AMPA/kainate Dopamine Glutamate Locomotor activity MK-801 NMDA Place conditioning Place preference Reward
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