Blockade of the metabotropic glutamate receptor subtype 5 (mGluR5) produces antiparkinsonian-like effects in rats

The aim of the present study was to examine a potential beneficial effect o f the blockade of metabotropic glutamate receptor subtype 5 (mGluR5) by the selective non-competitive antagonist, 2-methyl-6-(phenylethynyl)pyridine ( MPEP), in models of parkinsonian symptoms in rats. Haloperidol, 0.25, 0.5 a nd 1 mg/kg ip, was used to induce hypolocomotion, catalepsy and muscle rigi dity, respectively. The locomotor activity was estimated by an open-field t est, the catalepsy - by a 9-cm cork test. The muscle rigidity was measured as an increased resistance of a hind leg to passive extension and flexion a t the ankle joint. Additionally, increases in the electromyographic activit y were recorded in the gastrocnemius and tibialis anterior muscles. MPEP (1 .0-10 mg/kg ip) inhibited the muscle rigidity, electromyographic activity, hypolocomotion and catalepsy induced by haloperidol. MPEP administered alon e (5 mg/kg ip) did not induce catalepsy, nor did it influence the muscle to ne or locomotor activity in rats. The present results suggest that blockade of mGluR5 receptors may be important to amelioration of both parkinsonian akinesia and muscle rigidity. (C) 2001 Elsevier Science Ltd. All rights res erved.