Modulation of the locomotor responses induced by D1-like and D2-like dopamine receptor agonists and D-amphetamine by NMDA and non-NMDA glutamate receptor agonists and antagonists in the core of the rat nucleus accumbens.

Dopamine and glutamate interactions in the nucleus accumbens (NAcc) play a crucial role in both the development of a motor response suitable for the environment and in the mechanisms underlying the motor-activating properties of psychostimulant drugs such as amphetamine. We investigated the effects of the infusion in the NAcc of NMDA and non-NMDA receptor agonists and antagonists on the locomotor responses induced by the selective D(1)-like receptor agonist SKF 38393, the selective D(2)-like receptor agonist quinpirole, alone or in combination, and D-amphetamine. Infusion of either the NMDA receptor agonist NMDA, the NMDA receptor antagonist D-AP5, the non-NMDA receptor antagonist CNQX, or the non-NMDA receptor agonist AMPA resulted in an increase in basal motor activity. Conversely, all of these ionotropic glutamate (iGlu) receptor ligands reduced the increase in locomotor activity induced by focal infusion of D-amphetamine. Interactions with dopamine receptor activation were not so clear: (i). infusion of NMDA and D-AP5 respectively enhanced and reduced the increase in locomotor activity induced by the infusion of the D(1)-like receptor agonist of SKF 38393, while AMPA or CNQX decreased it; (ii). infusion of NMDA, D-AP5, and CNQX reduced the increase in locomotor activity induced by co-injection of SKF 38393+quinpirole--a pharmacological condition thought to activate both D(1)-like and D(2)-like presynaptic and postsynaptic receptors, while infusion of AMPA potentiated it; (iii). infusion of either NMDA, D-AP5 or CNQX, but not of AMPA, potentiated the decrease in motor activity induced by the D(2)-like receptor agonist quinpirole, a compound believed to act only at presynaptic D(2)-like receptors when injected by itself. Our results show that NMDA receptors have an agonist action with D(1)-like receptors and an antagonist action with D(2)-like receptors, while non-NMDA receptors have the opposite action. This is discussed from a anatamo-functional point of view.