Dopamine agonists potentiate antiakinetic effects of competitive NMDA-antagonists in monoamine-depleted mice

• Published in: Journal of Neural Transmission Vol. 84; no. 3; pp. 211 - 220
• Main Authors: KANNARI, K, MARKSTEIN, R
• Format: Journal Article
• Language: English
• Published: Wien Springer 01-01-1991; New York, NY
• Subjects: 2-Amino-5-phosphonovalerate - analogs & derivatives; 2-Amino-5-phosphonovalerate - pharmacology; 2-Amino-5-phosphonovalerate - therapeutic use; alpha-Methyltyrosine; Animals; Binding, Competitive; Biological and medical sciences; Caudate Nucleus - drug effects; Caudate Nucleus - physiopathology; Dopamine Agents - pharmacology; Dopamine Agents - therapeutic use; Drug Synergism; Dyskinesia, Drug-Induced - drug therapy; Fundamental and applied biological sciences. Psychology; Indoles - pharmacology; Indoles - therapeutic use; Male; Methyltyrosines - toxicity; Mice; Motor Activity - drug effects; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; N-Methylaspartate - antagonists & inhibitors; Piperazines - pharmacology; Piperazines - therapeutic use; Putamen - drug effects; Putamen - physiopathology; Receptors, Dopamine - classification; Receptors, Dopamine - drug effects; Receptors, Dopamine - physiology; Receptors, N-Methyl-D-Aspartate - drug effects; Reserpine - toxicity; Vertebrates: nervous system and sense organs; α2-Adrenergic receptor; Agonist; Dopamine; Dopamine receptor; Rodentia; Catecholamine; Glutamate; Locomotion; Vertebrata; Mammalia; Mouse; Antagonist; NMDA receptor; Motricity
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/BF01244971

The competitive NMDA-antagonists SDZ EAA-494 and CGP 37849 and the mixed D-1/D-2 dopamine agonists CI 201-678 and SDZ 205-152 reverse akinesia in monoamine-depleted mice in a dose dependent manner. Combination of threshold doses of NMDA-antagonists with dopamine agonists markedly enhances anti-akinetic effects. CI 201-678 which in addition to D-1 and D-2 receptors stimulates alpha-2 receptors produces a stronger effect than SDZ 205-152 which is devoid of alpha-2 agonist activity. The results indicate that concomitant blockade of NMDA-receptors and activation of dopamine receptors results in synergistic or at least additive motor stimulatory effects.