Dopamine-independent and adenosine-dependent mechanisms involved in the effects of N-methyl-D-aspartate on motor activity in mice.
The involvement of dopamine and adenosine mechanisms in the motor effects of systemically administered N-methyl-D-aspartate (NMDA) was studied in non-reserpinized and in reserpinized mice. In non-reserpinized mice NMDA induced motor depression (with 8, 25 and 75 mg/kg i.p.) during the first hour and motor activation (with 25 and 75 mg/kg i.p.) during the second hour after its administration. The non-selective adenosine antagonist, theophylline (3, 10 and 30 mg/kg i.p) induced motor activation during both 1-h periods of observation. NMDA-induced motor depression in non-reserpinized mice was antagonized by theophylline. Higher doses of theophylline were needed to counteract the motor depressant effect induced by higher doses of NMDA. The motor activation induced by NMDA and theophylline in non-reserpinized mice was not additive and theophylline did not enhance the motor activation induced by high doses of NMDA. Both NMDA (25 and 75 mg/kg i.p.) and theophylline (10 and 30 mg/kg) induced motor activation in reserpinized mice and, when coadministered, NMDA counteracted the effect of theophylline. NMDA (8 and 25 mg/kg i.p.) antagonized and theophylline (3, 10 and 30 mg/kg i.p.) potentiated the motor activation induced by the non-selective dopamine agonist, apomorphine (0.1 mg/kg s.c.), in reserpinized mice. In reserpinized mice, the non-selective dopamine antagonist, haloperidol (0.5 mg/kg s.c.) antagonized the motor activation induced by apomorphine (0.1 mg/kg s.c.) and the induced by theophylline (10 mg/kg i.p.) and did not modify NMDA-induced motor activation.(ABSTRACT TRUNCATED AT 250 WORDS)
Giménez-Llort
L
L
Department of Neurochemistry, C.S.I.C., Barcelona, Spain.
Martínez
E
E
Ferré
S
S
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004347:Drug Interactions; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000633:toxicity*; D012110:Reserpine / Q000008:administration & dosage / Q000494:pharmacology; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology
D018492:Dopamine Antagonists; D016202:N-Methylaspartate; D012110:Reserpine; D013806:Theophylline; D006220:Haloperidol; D000241:Adenosine; D001058:Apomorphine