NMDA RECEPTORS IN NUCLEUS-ACCUMBENS MODULATE STRESS-INDUCED DOPAMINE RELEASE IN NUCLEUS-ACCUMBENS AND VENTRAL TEGMENTAL AREA

Converging evidence suggests that dopamine (DA) transmission in nucleu s accumbens (NAcc) is modulated locally by an excitatory amino acid (E AA)containing input possibly originating in medial prefrontal cortex ( PFC). In the present study, we examined the effects of intra-NAcc admi nistration of EAA receptor antagonists on stress-induced increases of NAcc DA levels and of dendritically released DA in the ventral tegment al area (VTA). Local injection of the NMDA receptor antagonist-AP-5 (0 .05, 0.5, and 5.0 nmoles)-dose-dependently potentiated increases in NA cc DA levels elicited by 15 min of restraint stress. In contrast, loca l application of equivalent doses of the kainate/AMPA receptor antagon ist-DNQX-failed to alter the NAcc DA stress response reliably. In a se parate experiment, we found that intra-NAcc injection of AP-5 also pot entiated stress-induced increases in VTA DA levels. These results indi cate that EAAs acting at NMDA receptors in NAcc can modulate stress-in duced DA release in this region. Our data indicate, however, that this action exerts an inhibitory influence on the NAcc DA stress response, suggesting that the relevant population of NMDA receptors are not loc ated on NAcc DA terminals. The fact that intra-NAcc AP-5 injections al so potentiated the DA stress response in VTA suggests instead an actio n mediated by NMDA receptors located on NAcc neurons that feedback, di rectly or indirectly, to cell bodies of the mesocorticolimbic DA syste m. (C) 1997 Wiley-Liss, Inc.