N-METHYL-D-ASPARTATE AND DOPAMINE-RECEPTOR INVOLVEMENT IN THE MODULATION OF LOCOMOTOR-ACTIVITY AND MEMORY PROCESSES

In this study we report on the effects of N-methyl-D-aspartate (NMDA)- and dopamine (DA)-receptor manipulation on the modulation of one-tria l inhibitory avoidance response and the encoding of spatial informatio n, as assessed with a non-associative task. Further, a comparison with the well-known effects of the manipulation of these two receptor syst ems on locomotor activity is outlined. It is well assessed that NMDA-r eceptor blockage induces a stimulatory action on locomotor activity si milar to that exerted by DA agonists. There is evidence showing that t he nucleus accumbens is involved in the response induced by both NMDA antagonists and DA agonists. We show results indicating a functional i nteraction between these two neural systems in modulating locomotor ac tivity, with D2 DA-receptor antagonists (sulpiride and haloperidol) be ing more effective than the D1 antagonist (SCH 23390) in blocking MK-8 01-induced locomotion. A different profile is shown in the effects of NMDA antagonists and DA agonists in the modulation of memory processes . In one-trial inhibitory avoidance response, NMDA antagonists (MK-801 and CPP) impair the response on test day, while DA agonists exert a f acilitatory effect; furthermore, sub-effective doses of both D1 (SKF 2 3390) and D2 (quinpirole) are able to attenuate the impairing effect i n a way similar to that induced by NMDA antagonists. The effects of NM DA- and DA-acting drugs on the response to spatial novelty, as assesse d with a task designed to study the ability of animals to react to dis crete spatial changes, are in good accord with the effects observed on passive avoidance. The results show that NMDA as well as DA antagonis ts, at low doses, selectively impair the reactivity of mice to spatial changes. In a last series of experiments, the possible role of NMDA r eceptors located in the nucleus accumbens was investigated regarding r eactivity to spatial novelty. The experiments Save apparently contrast ing results: while showing an impairing effect of focal administration s of NMDA antagonists in the nucleus accumbens on reactivity to spatia l novelty, no effect of ibotenic acid lesions of the same structure wa s observed.