MTEP, a new selective antagonist of the metabotropic glutamate receptor subtype 5 (mGluR5), produces antiparkinsonian-like effects in rats K. Ossowska a, * , J. Konieczny a , S. Wolfarth a , A. Pilc b a Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Sme xtna St., 31-343 Krako ´w, Poland b Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, 12 Sme xtna St., 31-343 Krako ´w, Poland Received 21 October 2004; received in revised form 14 February 2005; accepted 5 April 2005 Abstract The aim of the present study was to examine a potential antiparkinsonian-like action of 3-[(2-methyl-1,3-thiazol-4- yl)ethynyl]pyridine (MTEP), a new non-competitive antagonist of mGluR5, in the rat models. This compound has affinity for mGluR5 in a nanomolar concentration range and seems to be superior to the earlier known antagonists in terms of its specificity and bioavailability. Catalepsy and muscle rigidity induced by haloperidol administered at doses of 0.5 and 1 mg/kg were regarded as models of parkinsonian akinesia and muscle rigidity, respectively. MTEP at doses between 0.5 and 3 mg/kg i.p. decreased the haloperidol-induced muscle rigidity measured as an increased muscle resistance of the rat’s hind leg in response to passive extension and flexion at the ankle joint. The strongest and the longest effect was observed after the dose of 1 mg/kg. MTEP (0.5e3 mg/kg i.p.) also reduced the haloperidol-induced increase in electromyographic (EMG) activity recorded in the gastrocnemius and tibialis anterior muscles. MTEP (3 and 5 mg/kg i.p.) inhibited the catalepsy induced by haloperidol. The present study confirms earlier suggestions that the antagonists of mGluR5 may possess antiparkinsonian properties. However, selective mGluR5 antagonists may be more effective in inhibiting parkinsonian muscle rigidity than parkinsonian akinesia. Ó 2005 Elsevier Ltd. All rights reserved. Keywords: Metabotropic receptor 5; Muscle rigidity; Catalepsy; Parkinsonism; Rat 1. Introduction The primary cause of Parkinson’s disease is de- generation of the dopaminergic nigrostriatal neurons which leads to a dramatic loss of dopamine in the corpus striatum (Ehringer and Hornykiewicz, 1960). Moreover, it has been suggested that dopaminergic deficiency may result in secondary overactivity of glutamatergic pathways which contributes to the development of parkinsonian symptoms (Klockgether and Turski, 1989). In line with this view, the antagonists of N- methyl-D-aspartate (NMDA) receptors induce antipar- kinsonian effects in humans and in animal models of this disease (for review see Ossowska, 1994). Glutamate acts on two main categories of recep- tors: (1) ionotropic (NMDA, AMPA and kainate) receptors, and (2) G-protein-coupled metabotropic re- ceptors (mGluRs). The mGluRs have been classified into three groups: group I (mGluR1 and mGluR5), group II (mGluR2 and mGluR3) and group III (mGluR4, mGluR6, mGluR7, mGluR8) (Schoepp et al., 1999). Receptors belonging to group I are excitatory, localized * Corresponding author. Tel.: C48 12 6623321; fax: C48 12 6374500. E-mail address: ossowska@if-pan.krakow.pl (K. Ossowska). 0028-3908/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropharm.2005.04.002 Neuropharmacology 49 (2005) 447e455 www.elsevier.com/locate/neuropharm