title: The role of reactive oxygen species in methamphetamine self-administration and dopamine release in the nucleus accumbens.
abstract: Methamphetamine (METH) markedly increases dopamine (DA) release in the mesolimbic DA system, which plays an important role in mediating the reinforcing effects of METH. METH-induced DA release results in the formation of reactive oxygen species (ROS), leading to oxidative damage. We have recently reported that ROS are implicated in behavior changes and DA release in the nucleus accumbens (NAc) following cocaine administration. The aim of this study was to evaluate the involvement of ROS in METH-induced locomotor activity, self-administration and enhancement of DA release in the NAc. Systemic administration of a non-specific ROS scavenger, N-tert-butyl-α-phenylnitrone (PBN; 0, 50 and 75 mg/kg, IP) or a superoxide-selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL; 0, 50 and 100 mg/kg, IP), attenuated METH-induced locomotor activity without affecting generalized behavior in METH-naïve rats. PBN and TEMPOL significantly attenuated METH self-administration without affecting food intake. Increased oxidative stress was found in neurons, but not astrocytes, microglia or oligodendrocytes, in the NAc of METH self-administering rats. In addition, TEMPOL significantly decreased METH enhancement of DA release in the NAc. Taken together, these results suggest that enhancement of ROS in the NAc contributes to the reinforcing effect of METH.
authors.affiliation: Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, UT, USA.|College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Jang
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Chae Ha
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, UT, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Hedges
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Soo Phil
authors.initials: SP
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Jun Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, UT, USA.
authors.forename: Tyler G
authors.initials: TG
authors.lastname: Ekins
authors.affiliation: Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, UT, USA.
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Garcia
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, UT, USA.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Nelson
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Nam Jun
authors.initials: NJ
authors.lastname: Kim
authors.affiliation: Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, UT, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Steffensen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012646:Self Administration; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D000697:Central Nervous System Stimulants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; D008694:Methamphetamine; C001803:tempol; D004298:Dopamine
keywords: PBN; TEMPOL; dopamine (DA); methamphetamine self-administration; nucleus accumbens; reactive oxygen species (ROS)