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 of 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 and 1mg/kg ip, was used to induce hypolocomotion, catalepsy and muscle rigidity, respectively. The locomotor activity was estimated by an open-field test, 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 at the ankle joint. Additionally, increases in the electromyographic activity were recorded in the gastrocnemius and tibialis anterior muscles. MPEP (1.0-10mg/kg ip) inhibited the muscle rigidity, electromyographic activity, hypolocomotion and catalepsy induced by haloperidol. MPEP administered alone (5mg/kg ip) did not induce catalepsy, nor did it influence the muscle tone 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.
Ossowska
K
K
Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St, 31-343 Kraków, Poland. ossowska@if-pan.krakow.pl
Konieczny
J
J
Wolfarth
S
S
Wierońska
J
J
Pilc
A
A
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000633:toxicity; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control; D004409:Dyskinesia, Drug-Induced / Q000517:prevention & control; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000633:toxicity; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009127:Muscle Rigidity / Q000139:chemically induced / Q000517:prevention & control; D009213:Myography; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine; D006220:Haloperidol