NMDA or AMPA/kainate receptor blockade prevents acquisition of conditioned place preference induced by D2/3 dopamine receptor stimulation in rats

Rationale: Recent experiments from this laboratory demonstrated synergistic effects of AMPA/kainate receptor blockade and D-2/3 dopamine (DA) receptor stimulation on brain stimulation reward and locomotor activity. Objectives: 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 D-2/3 DA receptor agonist 7-OH-DPAT. Results: Effects of these compounds, alone and combined, were measured in male Sprague-Dawley rats using an unbiased two-compartment place conditioning procedure. Results: 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) supercript stop, i.p.) or NBQX (0.5 mu g) microinjected into the nucleus accumbens (NAS) shell subregion. Intra-NAS shell administration of 7-OH-DPAT (5.0 mu g) or NBQX (0.5 mu g), 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) supercript stop) during the conditioning phase acutely increased horizontal activity, but neither compound, alone or combined, induced conditioned locomotor effects. Conclusions: 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.