Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist

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作者：

Ewa Tatarczyńska，Aleksandra K?odzińska，Ewa Chojnacka-Wójcik，Agnieszka Pa?ucha，F Gasparini，R Kuhn，A Pilc

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摘要：

Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of action of anxiolytic and/or antidepressant drugs. The involvement of group I mGlu receptors in anxiety and depression has also been proposed. Given the recent discovery of a selective and brain penetrable mGlu5 receptor antagonists, the effect of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), i.e. the most potent compound described, was evaluated in established models of anxiety and depression. Experiments were performed on male Wistar rats or male Albino Swiss or C57BL/6J mice. The anxiolytic-like effects of MPEP was tested in the conflict drinking test and the elevated plus-maze test in rats as well as in the four-plate test in mice. The antidepressant-like effect was estimated using the tail suspension test in mice and the behavioural despair test in rats. MPEP (1 30 mg kg 1 ) induced anxiolytic-like effects in the conflict drinking test and the elevated plus-maze test in rats as well as in the four-plate test in mice. MPEP had no effect on locomotor activity or motor coordination. MPEP (1 20 mg kg 1 ) did shorten the immobility time in a tail suspension test in mice, however it was inactive in the behavioural despair test in rats. These data suggest that selective mGlu5 receptor antagonists may play a role in the therapy of anxiety and/or depression, further studies are required to identify the sites and the mechanism of action of MPEP. British Journal of Pharmacology (2001) 132 , 14231430; doi: [DOI link]

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关键词：

mGlu5 receptors MPEP conflict drinking test four-plate test plus-maze test tail suspension test anxiety depression