PT  - JOURNAL ARTICLE
AU  - Spooren, Will P. J. M.
AU  - Vassout, Annick
AU  - Neijt, Hans C.
AU  - Kuhn, Rainer
AU  - Gasparini, Fabrizio
AU  - Roux, Silvain
AU  - Porsolt, Roger D.
AU  - Gentsch, Conrad
TI  - Anxiolytic-Like Effects of the Prototypical Metabotropic Glutamate Receptor 5 Antagonist 2-Methyl-6-(phenylethynyl)pyridine in Rodents
DP  - 2000 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1267--1275
VI  - 295
IP  - 3
4099  - http://jpet.aspetjournals.org/content/295/3/1267.short
4100  - http://jpet.aspetjournals.org/content/295/3/1267.full
SO  - J Pharmacol Exp Ther2000 Dec 01; 295
AB  - Recently, selective and systemically active antagonists for the metabotropic glutamate 5 receptor (mGlu5) were discovered, and the most potent derivative was found to be MPEP (2-methyl-6-(phenylethynyl)pyridine). Given the high expression of mGlu5 receptors in limbic forebrain regions, it was decided to evaluate the anxiolytic potential of MPEP. After an acute oral administration, MPEP attenuated the anxiety-dependent variable in a variety of well established anxiety test paradigms. In rats, MPEP (10, 30, and 100 mg/kg) increased punished responses in the Geller-Seifter test, but none of these effects reached statistical significance. MPEP significantly increased the ratio (open/total arm entries; 0.1, 1, and 10 mg/kg), the number of open arm entries (0.1, 1, and 10 mg/kg), as well as time spent on open arm (0.1 and 1 mg/kg) in the elevated plus maze test. Furthermore, MPEP (0.3 and 1 mg/kg) significantly increased the time spent in social contact in the social exploration test. In mice, MPEP attenuated stress-induced hyperthermia (15 and 30 mg/kg) and decreased the number of buried marbles in the marble burying test (7.5 and 30 mg/kg). Finally, MPEP (0.01, 0.1, 1, 10, and 100 mg/kg) was tested on spontaneous locomotor activity in mice, and only a dose of 100 mg/kg significantly reduced vertical activity; no effect was seen on horizontal activity. MPEP (7.5, 15, and 30 mg/kg) was ineffective ond-amphetamine-induced (2.5 mg/kg) locomotor activity in mice and prepulse inhibition in rats (1, 3, or 10 mg/kg). Thus, these findings indicate that MPEP exhibits anxiolytic-like effects and low risks for sedation and psychotomimetic side-effects in rodents. The American Society for Pharmacology and Experimental Therapeutics