title: The mGluR5 antagonist fenobam induces analgesic conditioned place preference in mice with spared nerve injury.
abstract: Antagonists of metabotropic glutamate receptors (mGluRs) have the potential to act as analgesic drugs that may help alleviate chronic pain. This study was done to look at the possible rewarding properties of the mGluR5 antagonist, fenobam, in a cognitive assay. Analgesic conditioned place preference (aCPP) was used to examine the effects of fenobam (30 mg/kg) and the prototypical mGluR5 antagonist, MPEP, and these effects were compared to those of a drug with known analgesic properties, morphine (10 mg/kg). In each experiment, one group of mice received spared nerve injury (SNI) surgery to model chronic pain; the other group received a control sham surgery. Both fenobam and MPEP induced preference in the SNI mice, such that SNI mice spent significantly more time in the mGluR5 antagonist-paired chamber compared to a vehicle-paired chamber. No such preference developed for sham mice. Morphine induced preference in male and female mice in both the SNI and sham groups. The results showed that fenobam and MPEP likely reduced on-going distress in the SNI mice, causing them to prefer the chamber paired with the drug compared to the vehicle-paired chamber. Since sham animals did not prefer the drug-paired chamber, these data demonstrate that mGluR5 antagonism is non-rewarding in the absence of pain-like injury.
authors: Department of Biological Sciences and Chronic Pain Research Consortium, Duquesne University, Pittsburgh, Pennsylvania, United States of America.
authors: Neil C
authors: NC
authors: Lax
authors: Department of Biological Sciences and Chronic Pain Research Consortium, Duquesne University, Pittsburgh, Pennsylvania, United States of America.
authors: David C
authors: DC
authors: George
authors: Department of Biological Sciences and Chronic Pain Research Consortium, Duquesne University, Pittsburgh, Pennsylvania, United States of America.
authors: Christopher
authors: C
authors: Ignatz
authors: Department of Biological Sciences and Chronic Pain Research Consortium, Duquesne University, Pittsburgh, Pennsylvania, United States of America.
authors: Benedict J
authors: BJ
authors: Kolber
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology; D059348:Peripheral Nerve Injuries / Q000503:physiopathology*; D011725:Pyridines / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors*
chemical_list: D000700:Analgesics; D018691:Excitatory Amino Acid Antagonists; C578936:Grm5 protein, mouse; D007093:Imidazoles; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; C032794:fenobam; D009020:Morphine; C121465:6-methyl-2-(phenylethynyl)pyridine