Intrastriatal injection of a selective metabotropic excitatory amino acid receptor agonist induces contralateral turning in the rat.

The consequence of in vivo activation of the phosphoinositide-coupled (metabotropic) excitatory amino acid (EAA) receptor subtype was investigated. We report that unilateral intrastriatal injection of 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), a selective metabotropic EAA receptor agonist, produced turning behavior (rotations) contralateral to the site of injection. This effect peaked at 5 to 8 hr after injection and was dose-related (EC50 = 0.59 mumol), producing a maximal effect at 1 mumol (32 +/- 4 rotations per 5 min). 1S,3R-ACPD-induced rotations were not mimicked by intrastriatal injection of vehicle (2 microliters of normal saline) or up to 2 mumol of 1R,3S-ACPD, the inactive ACPD isomer at the metabotropic EAA receptor. The selective competitive N-methyl-Daspartate receptor antagonist LY27461 4 (up to 5 mg/kg i.p) did not significantly affect 1S,3R-ACPD-induced rotations. However, coinjection of the metabotropic EAA receptor antagonist L-2-amino-3-phosphonopropionic acid (1 mumol) significantly reduced 1S,3R-ACPD-induced contralateral rotations. 1S,3R-ACPD at a dose which produced maximal contralateral rotations did not produce any loss of striatal gamma-aminobutyric acid neurons as indexed by glutamic acid decarboxylase enzyme activity in the injected striatum. In contrast to 1S,3R-ACPD, a dose of N-methyl-D-aspartate (0.2 mumol), which only very modestly induces contralateral rotations results in highly significant neuronal degeneration (50% loss of glutamic acid decarboxylase activity), and is associated with other excitatory behaviors such as clonic convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)