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.

METHODS

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), i.p.) or NBQX (0.5 microg) microinjected into the nucleus accumbens (NAS) shell subregion. Intra-NAS shell administration of 7-OH-DPAT (5.0 microg) or NBQX (0.5 microg), 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.

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.