title: Intrastriatal injection of a selective metabotropic excitatory amino acid receptor agonist induces contralateral turning in the rat.
abstract: 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)
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: A I
authors.initials: AI
authors.lastname: Sacaan
authors.forename: J A
authors.initials: JA
authors.lastname: Monn
authors.forename: D D
authors.initials: DD
authors.lastname: Schoepp
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D010875:Pipecolic Acids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014316:Tritium
chemical_list: D010716:Phosphatidylinositols; D010875:Pipecolic Acids; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D003515:Cycloleucine; D014316:Tritium; C036361:1-amino-1,3-dicarboxycyclopentane; C053672:selfotel