title: Morphine in combination with metabotropic glutamate receptor antagonists on schedule-controlled responding and thermal nociception.
abstract: The present study examined the interactive effects of morphine in combination with metabotropic glutamate (mGlu) receptor antagonists on schedule-controlled responding and thermal nociception. Drug interaction data were examined with isobolographic and dose-addition analysis. Morphine, the mGlu1 receptor antagonist JNJ16259685 [(3,4-dihydro-2H-pyrano-[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone], the mGlu5 receptor antagonist MPEP [2-methyl-6-(phenylethynyl)pyridine hydrochloride], and the mGlu2/3 receptor antagonist LY341495 [(2S)-2-amino-2-[(1S,2S-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid] all decreased rates of schedule-controlled responding. JNJ16259685/morphine, MPEP/morphine, and LY341495/morphine mixtures produced additive effects on this endpoint. Morphine also produced dose-dependent antinociception in the assay of thermal nociception, whereas JNJ16259685, MPEP, and LY341495 failed to produce an effect. In this assay, JNJ16259685 and LY341495 potentiated the antinociceptive effects of morphine, whereas MPEP/morphine mixtures produced additive effects. These results suggest that an mGlu1 and an mGlu2/3 receptor antagonist, but not an mGlu5 receptor antagonist, selectively enhance the antinociceptive effects of morphine. In addition, these data confirm that the behavioral effects of drug mixtures depend on the endpoint under study.
authors.affiliation: Department of Psychology, CB# 3270, Davie Hall, University of North Carolina, Chapel Hill, NC 27599-3270, USA. bfischer@email.unc.edu
authors.forename: Bradford D
authors.initials: BD
authors.lastname: Fischer
authors.forename: Eric I
authors.initials: EI
authors.lastname: Zimmerman
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Picker
authors.forename: Linda A
authors.initials: LA
authors.lastname: Dykstra
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D006358:Hot Temperature / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012055:Reinforcement Schedule
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D009020:Morphine