title: Double Dissociation of Monoacylglycerol Lipase Inhibition and CB1 Antagonism in the Central Amygdala, Basolateral Amygdala, and the Interoceptive Insular Cortex on the Affective Properties of Acute Naloxone-Precipitated Morphine Withdrawal in Rats.
abstract: Both CB1 receptor antagonism and agonism, in particular by 2-arachidonyl glycerol (2-AG), have been shown to reduce somatic symptoms of morphine withdrawal (MWD). Here we evaluated the effects of both systemic pretreatment with the monoacylglycerol lipase (MAGL) inhibitor MJN110 (which selectively elevates 2-AG) and central administration of both MJN110 and the CB1 antagonist (AM251) on the affective properties of MWD. Acute MWD induced place aversion occurs when naloxone is administered 24 h following a single exposure to a high dose of morphine. Systemic pretreatment with the MAGL inhibitor, MJN110, prevented the aversive effects of acute MWD by a CB1 receptor-dependent mechanism. Furthermore, in a double dissociation, AM251 infusions into the central amygdala, but MJN110 infusions into the basolateral amygdala, interfered with the naloxone-precipitated MWD induced place aversion. As well, MJN110, but not AM251, infusions into the interoceptive insular cortex (a region known to be activated in acute MWD) also prevented the establishment of the place aversion by a CB1 mechanism of action. These findings reveal the respective sites of action of systemically administered MJN110 and AM251 in regulating the aversive effects of MWD.
authors.affiliation: Collaborative Neuroscience Program, Department of Psychology, University of Guelph, Guelph, ON, Canada.
authors.forename: Kiri L
authors.initials: KL
authors.lastname: Wills
authors.affiliation: Collaborative Neuroscience Program, Department of Psychology, University of Guelph, Guelph, ON, Canada.
authors.forename: Gavin N
authors.initials: GN
authors.lastname: Petrie
authors.affiliation: Collaborative Neuroscience Program, Department of Psychology, University of Guelph, Guelph, ON, Canada.
authors.forename: Geneva
authors.initials: G
authors.lastname: Millett
authors.affiliation: Collaborative Neuroscience Program, Department of Psychology, University of Guelph, Guelph, ON, Canada.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Limebeer
authors.affiliation: Collaborative Neuroscience Program, Department of Psychology, University of Guelph, Guelph, ON, Canada.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Rock
authors.affiliation: Skaggs Institute for Chemical Biology, Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Niphakis
authors.affiliation: Skaggs Institute for Chemical Biology, Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
authors.affiliation: Collaborative Neuroscience Program, Department of Psychology, University of Guelph, Guelph, ON, Canada.
authors.forename: Linda A
authors.identifier: 0000-0002-3494-9754
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000679:Amygdala / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D063388:Endocannabinoids / Q000494:pharmacology; D005989:Glycerides / Q000494:pharmacology; D008297:Male; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors; D009020:Morphine / Q000633:toxicity; D009270:Naloxone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009294:Narcotics / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology*; D013388:Succinimides / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D002219:Carbamates; D063388:Endocannabinoids; D005989:Glycerides; C587715:MJN110; D009292:Narcotic Antagonists; D009294:Narcotics; D013388:Succinimides; D009270:Naloxone; D009020:Morphine; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases