title: Involvement of reactive oxygen species in cocaine-taking behaviors in rats.
abstract: Reactive oxygen species (ROS) have been implicated in the development of behavioral sensitization following repeated cocaine exposure. We hypothesized that increased ROS following cocaine exposure would act as signaling molecules in the mesolimbic dopamine (DA) system, which might play an important role in mediating the reinforcing effects of cocaine. The aim of this study was to evaluate cocaine enhancement of brain metabolic activity and the effects of ROS scavengers on cocaine self-administration behavior, cocaine-induced ROS production in the nucleus accumbens (NAc) and cocaine enhancement of DA release in the NAc. Metabolic neural activity monitored by temperature and oxidative stress were increased in NAc following cocaine exposure. Systemic administration of the ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), either pre- or post-treatment, significantly decreased cocaine self-administration without affecting food intake. Infusion of TEMPOL into the NAc inhibited cocaine self-administration. Increased oxidative stress was found mainly on neurons, but not astrocytes, microglia or oligodendrocytes, in NAc of rats self-administering cocaine. TEMPOL significantly attenuated cocaine-induced enhancement of DA release in the NAc, compared to saline controls. TEMPOL had no effect on the enhancement of DA release produced by the DA transporter inhibitor GBR12909. Taken together, these findings suggest that enhancement of ROS production in NAc neurons contributes to the reinforcing effect of cocaine.
authors: College of Korean Medicine, Daegu Haany University, South Korea.|Department of Psychology, Center for Neuroscience, Brigham Young University, Provo, UT, USA.
authors: Eun Young
authors: EY
authors: Jang
authors: Acupuncture, Moxibustion & Meridian Research Center, Division of Standard Research, Korea Institute of Oriental Medicine, South Korea.
authors: Yeon-Hee
authors: YH
authors: Ryu
authors: College of Korean Medicine, Daegu Haany University, South Korea.
authors: Bong Hyo
authors: BH
authors: Lee
authors: College of Korean Medicine, Daegu Haany University, South Korea.
authors: Su-Chan
authors: SC
authors: Chang
authors: College of Korean Medicine, Daegu Haany University, South Korea.
authors: Mi Jin
authors: MJ
authors: Yeo
authors: College of Korean Medicine, Daegu Haany University, South Korea.
authors: Sang Hyun
authors: SH
authors: Kim
authors: Department of Psychology, Center for Neuroscience, Brigham Young University, Provo, UT, USA.
authors: Ryan J
authors: RJ
authors: Folsom
authors: Department of Psychology, Center for Neuroscience, Brigham Young University, Provo, UT, USA.
authors: Nathan D
authors: ND
authors: Schilaty
authors: College of Korean Medicine, Daegu Haany University, South Korea.
authors: Kwang Joong
authors: KJ
authors: Kim
authors: College of Korean Medicine, Daegu Haany University, South Korea.
authors: Chae Ha
authors: CH
authors: Yang
authors: Department of Psychology, Center for Neuroscience, Brigham Young University, Provo, UT, USA.
authors: Scott C
authors: SC
authors: Steffensen
authors: College of Korean Medicine, Daegu Haany University, South Korea.
authors: Hee Young
authors: HY
authors: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000209:etiology*; D003216:Conditioning, Operant; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012055:Reinforcement Schedule; D012646:Self Administration; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D018765:Dopamine Uptake Inhibitors; D018696:Neuroprotective Agents; D010879:Piperazines; D017382:Reactive Oxygen Species; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; C043425:vanoxerine; D003042:Cocaine; C001803:tempol; D004298:Dopamine
keywords: Cocaine self-administration; NAc; TEMPOL; reactive oxygen species; reinforcing effect