title: Effects of isoflurane anesthesia and intravenous morphine self-administration on regional glucose metabolism ([18F]FDG-PET) of male Sprague-Dawley rats.
abstract: Although certain drugs of abuse are known to disrupt brain glucose metabolism (BGluM), the effects of opiates on BGluM are not well characterized. Moreover, preclinical positron emission tomography (PET) studies anesthetize animals during the scan, which limits clinical applications. We investigated the effects of (i) isoflurane anesthesia and (ii) intravenous morphine self-administration (MSA) on BGluM in rats. Jugular vein cannulated adult male Sprague-Dawley rats self-administered either saline (SSA) or morphine (0.5 mg/kg/infusion, 4 h/day for 12 days). All animals were scanned twice with [18F]-fluoro-deoxy-glucose (FDG)-PET/CT at a baseline and at 2-day withdrawal from self-administration. After the IV injection of FDG, one batch of animals (n = 14) was anesthetized with isoflurane and the other batch (n = 16) was kept awake during the FDG uptake (45 min). After FDG uptake, all animals were anesthetized in order to perform a PET/CT scan (30 min). Isoflurane anesthesia, as compared to the awake condition, reduced BGluM in the olfactory, cortex, thalamus, and basal ganglia, while increasing BGluM in the midbrain, hypothalamus, hippocampus, and cerebellum. Morphine self-administered animals exhibited withdrawal signs (piloerection and increased defecation), drug seeking, and locomotor stimulation to morphine (0.5 mg/kg) during the 2 day withdrawal. The BGluM in the striatum was increased in the MSA group as compared to the SSA group; this effect was observed only in the isoflurane anesthesia, not the awake condition. These findings suggest that the choice of the FDG uptake condition may be important in preclinical PET studies and increased BGluM in the striatum may be associated with opiate seeking in withdrawal.
authors.affiliation: Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.|Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Thomas Y
authors.initials: TY
authors.lastname: Park
authors.affiliation: Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.|Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Nishida
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Department of Radiology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Wilson
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Jaiswal
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Scott
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hoy
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Department of Radiology, University of New Mexico, Albuquerque, NM, USA.|Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Reed G
authors.initials: RG
authors.lastname: Selwyn
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Dardzinski
authors.affiliation: Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.|Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Graduate School of Nursing, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Kwang H
authors.identifier: 0000-0003-2884-4996
authors.initials: KH
authors.lastname: Choi
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000771:Anesthesia, Intravenous / Q000009:adverse effects; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D007530:Isoflurane / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000072078:Positron Emission Tomography Computed Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000209:etiology
chemical_list: D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D009020:Morphine; D007530:Isoflurane
keywords: brain energy metabolism; brain imaging; drug self-administration; opiate addition