Opposite influence of MPEP, an mGluR5 antagonist, on the locomotor hyperactivity induced by PCP and amphetamine.
Potential antipsychotic effects of a selective non-competitive antagonist of metabotropic glutamate receptor 5 (mGluR5), 2-methyl-6-phenylethynylpyridine (MPEP), was examined in two commonly used screening tests: (1) the hyperactivity induced by an NMDA receptor antagonist phencyclidine (PCP), and (2) the hyperactivity induced by an indirect dopamine agonist, D-amphetamine. PCP was administered at a dose of 2.5 mg/kg s.c. and D-amphetamine was given at a dose of 1 mg/kg s.c. MPEP (5 mg/kg i.p.) significantly enhanced the locomotor activity increased by PCP, but inhibited amphetamine-induced hyperactivity. The opposite effect of MPEP in the two above-mentioned models questions significance of the blockade of mGluR5 receptors to antipsychotic effects.
Pietraszek
M
M
Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Rogóz
Z
Z
Wolfarth
S
S
Ossowska
K
K
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003913:Dextroamphetamine; D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D006948:Hyperkinesis / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010622:Phencyclidine; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
D014150:Antipsychotic Agents; D015259:Dopamine 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; D010622:Phencyclidine; D003913:Dextroamphetamine