Effect of N-methyl-D-aspartate on motor activity and in vivo adenosine striatal outflow in the rat

It has been previously found that the systemic administration of low doses of N-methyl-D-aspartate (NMDA) in mice induces motor depression. The effect s of the systemic administration of different doses of NMDA (10, 30 and 60 mg/kg s.c.) on the motor activity and on the in vivo extracellular levels o f adenosine in the striatum was studied in Sprague-Dawley rats. The adenosi ne concentration in samples of perfusate was determined 24 h after implanta tion of a transverse microdialysis probe. At 30 and 60 mg/kg, but not 10 mg /kg, NMDA induced both a significant motor depression (motility and rearing ) and a significant increase in the striatal extracellular levels of adenos ine. Both the motor depression and the changes in the extracellular levels of adenosine were only evident during the first 30 min after NMDA administr ation. The non-competitive NMDA receptor antagonist MK-801 (0.1 mg/kg s.c.) completely counteracted the effects of NMDA (30 mg/kg s.c.) on motor activ ity (motility) and on the striatal extracellular levels of adenosine. The c orrelation between the behavioural and the biochemical data strongly suppor t the hypothesis that adenosine release in the striatum is a main mechanism responsible for the motor depressant effects produced by the systemic admi nistration of NMDA. (C) 1999 Elsevier Science B.V. All rights reserved.