In vivo inhibition of veratridine-evoked release of striatal excitatory amino acids by the group II metabotropic glutamate receptor agonist LY354740 in rats.
In vivo microdialysis in freely moving rats was used to investigate the presynaptic mechanisms by which LY354740, a novel, potent, selective, and systemically active agonist for group II metabotropic glutamate receptors (mGluRs), alters glutamate neuronal transmission. Basal levels of glutamate and aspartate in striatal dialysates of LY354740 (10 mg/kg i.p.)-treated animals were not significantly different from the saline-treated control animals. In the saline treated controls, veratridine (100 microM) induced a 6-fold increase in glutamate and 9-fold increase in aspartate. However, following LY354740 administration the veratridine-evoked release of glutamate and aspartate was completely prevented. These data demonstrate that LY354740 blocks the evoked release of endogenous excitatory amino acids, and indicate a role for group II mGluRs in presynaptic modulation of glutamate neuronal transmission in vivo. Ireland Ltd.
Battaglia
G
G
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Monn
J A
JA
Schoepp
D D
DD
D000818:Animals; D001224:Aspartic Acid / Q000032:analysis / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000032:analysis / Q000494:pharmacology*; D003342:Corpus Striatum / Q000737:chemistry* / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000032:analysis / Q000494:pharmacology*; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D014701:Veratridine / Q000494:pharmacology
D001643:Bridged Bicyclo Compounds; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D001224:Aspartic Acid; D018698:Glutamic Acid; D014701:Veratridine; C104753:eglumetad