Behavioral characterization of the mGlu group II/III receptor antagonist, LY-341495, in animal models of anxiety and depression.
There is a growing body of evidence indicating that stimulation of metabotropic glutamate type II receptors (mGlu2/3) reduces anxiety in laboratory animals and humans. Surprisingly, it was reported that mGlu2/3 receptor antagonists have antidepressant- and anxiolytic-like activities in laboratory animal studies as well. The present study aimed to resolve this controversy by characterizing behavioral effects of a selective mGlu2/3 receptor antagonist, LY-341495, in a variety of animal models sensitive to clinically used anxiolytic and antidepressant agents. In agreement with previous reports, LY-341495 (0.3-3 mg/kg, i.p.) reduced immobility in the mouse forced swim test. LY-341495 was also effective in the marble burying test in mice, although similar effects were observed after administration of various drugs including methamphetamine. Further, LY-341495 had no effects in the elevated plus maze and stress-induced hyperthermia tests in mice, as well as on punished drinking (Geller-Seifter's test) and differential reinforcement of low rates of responding (DRL) in rats. It is concluded that behavioral profile of mGlu2/3 receptor antagonists as represented by LY-341495 is different from that of conventional anxiolytic and antidepressant drugs.
Bespalov
Anton Y
AY
Neuroscience Discovery, GPRD, Abbott, P.O. Box 21 08 05, 67008 Ludwigshafen, Germany. anton.bespalov@abbott.com
van Gaalen
Marcel M
MM
Sukhotina
Irina A
IA
Wicke
Karsten
K
Mezler
Mario
M
Schoemaker
Hans
H
Gross
Gerhard
G
D000596:Amino Acids / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003624:Darkness; D003863:Depression / Q000188:drug therapy* / Q000523:psychology*; D003975:Diazepam / Q000494:pharmacology; D005334:Fever / Q000503:physiopathology / Q000523:psychology; D005473:Fluoxetine / Q000494:pharmacology; D008027:Light; D008297:Male; D051379:Mice; D017374:Paroxetine / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D013315:Stress, Psychological / Q000503:physiopathology / Q000523:psychology; D014966:Xanthenes / Q000494:pharmacology*
D000596:Amino Acids; D014151:Anti-Anxiety Agents; D018687:Antidepressive Agents, Second-Generation; D000697:Central Nervous System Stimulants; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D005473:Fluoxetine; D017374:Paroxetine; D000661:Amphetamine; D003975:Diazepam