Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats.
Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of action of anxiolytic and antidepressant drugs. The involvement of group I mGlu receptors in anxiety and depression has also been proposed. In view of the recent discovery of anxiolytic- or antidepressant-like effects of acute injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective and brain penetrable mGlu5 receptor antagonist, we designed the present study to examine anxiolytic- and/or antidepressant-like effects of multiple administrations of this drug. The anxiolytic-like effects of MPEP were evaluated in rats using the conflict drinking test. The antidepressant-like effect was estimated using the rat olfactory bulbectomy model of depression. Seven subsequent injections of MPEP (1 mg/kg) significantly (by 320%) increased the number of shocks accepted during the experimental session in the Vogel test. MPEP given once daily at a dose of 10 mg/kg, restored the learning deficit of bulbectomized rats after 14 days of treatment, remaining without any effect in the sham-operated animals. N-methyl-D-aspartic acid (NMDA)-induced convulsions in mice were not affected by a single injection of MPEP (30 mg/kg) indicating that at this dose MPEP did not block NMDA receptors. The results indicate that the prolonged blockade of mGlu5 receptors exerts anxiolytic- and antidepressant-like effects in rats. No tolerance to anxiolytic-like action occurs. The previously mentioned results further indicate that antagonists of group I mGlu receptors may play a role in the therapy of both anxiety and depression.
Pilc
A
A
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland. nfpilc@cyf-kr.edu.pl
Kłodzińska
A
A
Brański
P
P
Nowak
G
G
Pałucha
A
A
Szewczyk
B
B
Tatarczyńska
E
E
Chojnacka-Wójcik
E
E
Wierońska
J M
JM
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001007:Anxiety / Q000188:drug therapy; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D003863:Depression / Q000188:drug therapy; D008297:Male; D051379:Mice; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D011725:Pyridines; C121465:6-methyl-2-(phenylethynyl)pyridine