GLUTAMATE-DOPAMINE INTERACTIONS IN THE VENTRAL STRIATUM - ROLE IN LOCOMOTOR-ACTIVITY AND RESPONDING WITH CONDITIONED REINFORCEMENT

Previous evidence suggests that glutamatergic limbic afferents partici pate in the potentiation of responding with conditioned reinforcement produced by intra-accumbens d-amphetamine. The present experiments wer e designed to investigate glutamate-dopamine interactions in the ventr al striatum in both conditioned reinforcement and locomotor activity. Glutamate receptor agonists and antagonists were infused into the nucl eus accumbens both alone and in combination with 3 mu g d-amphetamine, and the effects of these interactions on responding with conditioned reinforcement and locomotor activity were measured. The glutamate rece ptor agonists NMDA, AMPA and quisqualate (agonists at the NMDA, AMPA a nd metabotropic glutamate receptor subtypes, respectively) and the ant agonists AP5 and CNQX, (antagonists at the NMDA and AMPA receptor subt ypes, respectively) were used in these investigations. These compounds were used in a dose range of 0.3 to 3 nmol, except CNQX, which was us ed in 0.2 to 2 nmol doses. While all agonists and antagonists increase d locomotor activity when administered alone, the antagonists attenuat ed the locomotor response to d-amphetamine. In contrast, the agonists AMPA and quisqualate enhanced d-amphetamine-induced locomotor activity , although NMDA interfered with the effects of d-amphetamine. In the c onditioned reinforcement paradigm, both the agonists and the antagonis ts abolished amphetamine's potentiation of responding with conditioned reinforcement, suggesting that the glutamatergic transmission of info rmation about the conditioned reinforcer could be blocked by glutamate receptor antagonists and disrupted by administration of the agonists. The dissociation between the effects of these excitatory amino acids on amphetamine-induced locomotor activity versus their effects on amph etamine's potentiation of responding with conditioned reinforcement pr ovides insight into the nature of the reward enhancement by accumbens dopamine versus its locomotor stimulant effects.