Selective mGlu5 receptor antagonist MTEP attenuates naloxone-induced morphine withdrawal symptoms.
Several lines of evidence suggest a crucial involvement of glutamate in the mechanism of drug addiction. The involvement of group I mGlu receptors in the mechanism of addiction has also been proposed. Given the recent discovery of selective and brain penetrable mGlu5 receptor antagonists, the effects of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) were evaluated in the naloxone-precipitated morphine withdrawal model. Experiments were performed on male C57BL/6J (20-25 g) mice. Mice were rendered morphine-dependent and withdrawal was precipitated with naloxone. Two hours and 15 min after the last dose of morphine, mice were injected with a mGlu5 receptor antagonist. MTEP (1-10 mg/kg) in a dose-dependent manner inhibited the naloxone-induced symptoms of morphine withdrawal in morphine-dependent mice, remaining without any effect on the locomotor activity of mice. The data suggest that selective mGlu5 receptor antagonists may play a role in the therapy of drug-dependence states.
Pałucha
Agnieszka
A
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
Brański
Piotr
P
Pilc
Andrzej
A
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000188:drug therapy; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects; D011725:Pyridines / Q000627:therapeutic use*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D013844:Thiazoles / Q000627:therapeutic use*
C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D009292:Narcotic Antagonists; D009294:Narcotics; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; D009270:Naloxone; D009020:Morphine