DOPAMINE-N-METHYL-D-ASPARTATE INTERACTIONS IN THE MODULATION OF LOCOMOTOR-ACTIVITY AND MEMORY CONSOLIDATION IN MICE

This study explores the functional interaction between glutamatergic a nd dopaminergic systems in the modulation of two behavioral responses: locomotor activity and memory consolidation assessed with one-trial i nhibitory avoidance. In agreement with previous reports, the NMDA rece ptor antagonist, (+)-MK-801 -5-methyl-10,11-dihydro(a,d)cyclohepten-5, 10-imine hydrogen maleate), dose dependently enhanced locomotor activi ty in mice. The selective dopamine D-1 receptor antagonist SCH 23390 a t doses up to 0.05 mg/kg was unable to affect MK-801-induced locomotor activity, while (-)-sulpiride, but only at high doses (30 mg/kg), and haloperidol (0.05 mg/kg) blocked the MK-801 effect. Hypermotility ind uced by MK-801 was enhanced by repeated administration of haloperidol (once daily administration for 14 days of 4 mg/kg) or (-)-sulpiride (1 25 mg/kg), but not SCH 23390 (0.5 mg/kg). Dopamine D-1 (SKF 38393)- an d D-2 (quinpirole)-selective agonists enhanced retention of one-trial inhibitory avoidance performance whilst NMDA receptor antagonists 3-(2 -D-carboxypiperazin-4-yl)propyl-1-phosphoric acid (CPP) and MK-801 imp aired it. Moreover we observed that the NMDA receptor antagonist-induc ed impairment of memory consolidation was attenuated by subeffective d oses of SKF 38393 (5 mg/kg) and quinpirole (0.25 mg/kg). Impairment of the response induced by post-trial injections of CPP and MK-801, in t he one-trial inhibitory avoidance test, was highly enhanced by 14 days of daily administration of haloperidol (4 mg/kg), sulpiride (25 mg/kg ) but also SCH 23390 (0.5 mg/kg). These results suggest that different neural mechanisms underlie the functional interaction between the two neural systems in the modulation of these behavioral responses. Furth er, the results of the chronic study revealed a possible heterologous regulation of NMDA receptors.