Involvement of ionotropic glutamate receptors in the appearance of arecoline tremor in mice.
Administration of the muscarinic cholinoreceptor agonist arecoline (6 mg/kg, s.c.) to mice induced long-lasting tremor. The ability of non-competitive antagonists of ionotropic glutamate receptors to suppress the onset of tremor was studied. These antagonists, i.e., adamantane and phenylcyclohexyl derivatives, selectively blocked NMDA-type receptor channels (monocations) or both NMDA-and AMPA-type channels (dications). Both types of blocker weakened arecoline tremor, though the dose-response relationships were different for mono-and dications. The effects of dications appeared only at low blocker doses (0.0001-0.01 micromol/kg) but gradually disappeared on dose elevation. These data lead to the conclusion that the mechanism of pathogenesis of arecoline tremor predominantly involves NMDA-type receptors. Moderate blockade of AMPA-type receptors could potentiate the preventive effect of mixed-action antagonists (anti-NMDA+anti-AMPA), though predominance of blocking action against AMPA-type receptors prevented this effect.
Lukomskaya
N Ya
NY
I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 M. Torez Prospekt, 194223 St. Petersburg, Russia.
Lavrent'eva
V V
VV
Starshinova
L A
LA
Zhabko
E P
EP
Gmiro
V E
VE
Magazanik
L G
LG
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001115:Arecoline; D003514:Cyclohexylamines / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D051379:Mice; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D014202:Tremor / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
D003514:Cyclohexylamines; D018691:Excitatory Amino Acid Antagonists; D000644:Quaternary Ammonium Compounds; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D001115:Arecoline; D000218:Adamantane