Metabotropic and ionotropic excitatory amino acid receptor agonists induce different behavioral effects in mice

Intracerebroventricular (i.c.v.) infusion in mice of the selective metabotropic excitatory amino acid receptor agonist 1S,3R-1- aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD) (0.6-575 nmol/min) dose dependently induced face washing and scratching. In contrast, the subtype-specific ionotropic excitatory amino acid receptor agonists N-methyl-D-aspartate (NMDA), kainate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) (0.3-3.0 nmol/min) dose dependently induced clonic convulsions. I.c.v. infusion of the non-selective metabotropic receptor agonists ibotenate (6 nmol/min) or quisqualate (30 nmol/min) induced clonic convulsions. However, when ionotropic receptors were blocked with (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)cyclohepten-5,10-imine maleate (MK-801, dizoclipine) (3 nmol/min) or 2,3-dihydroxy-6-nitro-7- sulfamoyl-benzo(f)-quinoxaline (NBQX) (9 nmol/min), respectively, face washing and scratching behavior emerged. Neither MK-801 or NBQX (ED50 value > 100 nmol/min), nor the putative metabotropic receptor antagonist L-amino-3-phosphoro-propionic acid (L-AP3) (> 176 nmol/min); nor the dopamine receptor antagonists SCH 23390 (> 74 nmol/min), metoclopramide (> 89 nmol/min) and haloperidol (> 27 nmol/min) antagonized 1S,3R-ACPD-induced scratching (144 nmol/min). These results suggest that the behavioral consequences of i.c.v. infusion of 1S,3R-ACPD in mice reflect a selective activation of metabotropic receptors that differs from the behavioral changes observed with i.c.v. infusion of ionotropic receptor agonists.