Effects of the mGlu2/3 receptor agonist LY379268 on motor activity in phencyclidine-sensitized rats.
Previous work has shown that mGlu2/3 receptor agonists such as LY379268 inhibit motor responses to acutely administered phencyclidine (PCP) in rats. However, it has not been determined whether mGlu2/3 receptor agonists will reverse the enhanced effects of repeatedly administered PCP (so called PCP sensitization). In these studies, rats were administered daily PCP and monitored for the number of ambulations, fine movements, time at rest and rears using an automated activity system. At Day 10, when compared the first (Day 1) response, PCP-treated animals showed enhanced responses to all measures tested. Augmentations of these PCP-induced behaviors generally peaked between the third and tenth day after PCP administration had begun. Acute administration of LY379268 effectively suppressed PCP-evoked motor behaviors in rats sensitized to PCP. However, daily administrations of LY379268 (for 9 days), along with PCP, did not prevent the expression of the enhanced PCP response on Day 10. Thus, LY379268 administration can suppress PCP responses after either acute or chronic exposure to PCP. However, the underlying plasticity that leads to PCP sensitization was not affected by this treatment.
Neuroscience Research Division, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Mail Drop 0510, Indianapolis, IN 46285, USA.
Matthew
M
Clark
Bryan G
BG
Johnson
Rebecca A
RA
Wright
James A
JA
Monn
Darryle D
DD
Schoepp
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D010622:Phencyclidine / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy
D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D010622:Phencyclidine