title: C-Fos activation in the periaqueductal gray following acute morphine-3β-D-glucuronide or morphine administration.
abstract: Morphine-3β-D-glucuronide (M3G), a primary morphine metabolite, evokes hyperalgesia in mice and rats and putatively mediates hyperalgesia associated with morphine (MOR) administration. However, M3G does not act via opioid receptors and its locus of activity in the CNS is unknown. Here we assessed the density of neurons immunoreactive for c-Fos, an immediate early gene regulated by neuronal activity, in the periaqueductal gray (PAG), a midbrain region critical to pain modulation, in male CD-1 mice after MOR and M3G exposure. Mice were injected with acute doses of MOR or M3G following a pre-injection of saline (SAL) or the opioid antagonist naltrexone (NTX), perfused 3 h later, and labeled for c-Fos using immunohistochemistry. Labeled image stacks taken from the PAG were then analyzed on a confocal microscope for the number of neurons showing c-Fos expression. Relative to controls, significant but similar increases in the mean density of PAG c-Fos immunoreactive neurons were observed in mice pre-injected with SAL then M3G or morphine. However, NTX pre-injection blocked this increase in MOR but not M3G injected mice. The data demonstrate for the first time a CNS locus for M3G activity. Consistent with previous observations, this M3G activity is not mediated by opioid receptors.
authors.affiliation: Neuropsychology Doctoral Subprogram, The Graduate Center, City University of New York, 365 5th Avenue, New York, NY 10016, United States. Electronic address: Caroline.Arout@csi.cuny.edu.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Arout
authors.affiliation: Center for Developmental Neuroscience, The College of Staten Island, City University of New York, 2800 Victory Boulevard, Staten Island, NY 10314, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Caldwell
authors.affiliation: Neuropsychology Doctoral Subprogram, The Graduate Center, City University of New York, 365 5th Avenue, New York, NY 10016, United States; Center for Developmental Neuroscience, The College of Staten Island, City University of New York, 2800 Victory Boulevard, Staten Island, NY 10314, United States; Department of Psychology, The College of Staten Island, City University of New York, 2800 Victory Boulevard, Staten Island, NY 10314, United States.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: McCloskey
authors.affiliation: Neuropsychology Doctoral Subprogram, The Graduate Center, City University of New York, 365 5th Avenue, New York, NY 10016, United States; Center for Developmental Neuroscience, The College of Staten Island, City University of New York, 2800 Victory Boulevard, Staten Island, NY 10314, United States; Department of Psychology, The College of Staten Island, City University of New York, 2800 Victory Boulevard, Staten Island, NY 10314, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kest
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D009020:Morphine / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011897:Random Allocation
chemical_list: D000697:Central Nervous System Stimulants; D009022:Morphine Derivatives; D009292:Narcotic Antagonists; D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D009271:Naltrexone; D009020:Morphine; C018108:morphine-3-glucuronide
keywords: Hyperalgesia; Morphine; Morphine-3β-d-glucuronide; Periaqueductal gray; c-Fos