Metabotropic excitatory amino acid receptor agonists selectively potentiate behavioral effects induced by ionotropic excitatory amino acid receptor agonists in mice.
The behavioral consequences of co-activation of metabotropic and ionotropic excitatory amino acid receptors were studied in mice using intracerebroventricular (i.c.v.) co-infusion of the metabotropic receptor agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD) with the subtype-specific ionotropic receptor agonists N-methyl-D-aspartate (NMDA), kainate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). I.c.v. co-infusion of ionotropic receptor agonists (0.3-3 nmol/min) with a fixed dose of 1S,3R-ACPD (144 nmol/min) decreased time to onset of clonic convulsions (P < 0.05). Pretreatment with i.c.v. infusion of 72 nmol of 1S,3R-ACPD reduced time to onset of convulsions induced by an intravenous (i.v.) infusion of NMDA (P < 0.05) but had no effect on convulsions induced by pentylenetetrazol. These results reveal that activation of the metabotropic excitatory amino acid receptor selectively potentiates the behavioral response following activation of the ionotropic excitatory amino acid receptors.
Klitgaard
H
H
Department of Neurophysiology, Novo Nordisk A/S, Måløv, Denmark.
Laudrup
P
P
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D009498:Neurotoxins; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid; D010433:Pentylenetetrazole