Article

Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats.

Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
Neuropharmacology (impact factor: 4.81). 09/2002; 43(2):181-7. pp.181-7
Source: PubMed

ABSTRACT 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.

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Keywords

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antidepressant drugs
 
antidepressant-like effect
 
anxiolytic-
 
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brain penetrable mGlu5 receptor antagonist
 
bulbectomized rats
 
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learning deficit
 
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NMDA)-induced convulsions
 
prolonged blockade
 
rat olfactory bulbectomy model
 
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subsequent injections