title: Subchronic apocynin treatment attenuates methamphetamine-induced dopamine release and hyperactivity in rats.
abstract: OBJECTIVE
  The effects of methamphetamine are linked to stimulation of dopaminergic neurons, which can be accompanied by production of reactive oxygen species (ROS). Apocynin (4-hydroxy-3-methoxy-acetophenone) is a nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase (NOX) inhibitor shown to mitigate oxidative stress in a number of models. The present study aimed at testing whether apocynin suppresses the dopamine-releasing and locomotor-activating properties of methamphetamine.
  
  
  METHODS
  (1) Apocynin (0.01-100μM) was applied to rat striatal slices preloaded with [(3)H]dopamine and its efficacy to evoke [(3)H]overflow and to alter methamphetamine (3μM)-evoked [(3)H]overflow was measured. (2) Groups of rats received apocynin (15 or 50mg/kg/day) or vehicle injection for seven consecutive days, and the efficacy and potency of methamphetamine to evoke [(3)H]overflow were determined. (3) Groups of apocynin-treated rats were administered methamphetamine (0.5 or 1mg/kg) or saline to determine the effect of apocynin on stimulant-induced hyperactivity.
  
  
  RESULTS
  (1) Apocynin applied to striatal slices did not evoke [(3)H]overflow or alter methamphetamine-evoked [(3)H]overflow. (2) However, subchronic apocynin treatment significantly and dose-dependently decreased methamphetamine's potency and efficacy to evoke [(3)H]overflow. (3) Subchronic apocynin treatment also decreased the locomotor activity evoked by methamphetamine.
  
  
  CONCLUSIONS
  Subchronic apocynin treatment diminished methamphetamine induced dopamine-release and its locomotor-activating properties. The pattern of results indicates that apocynin is more effective after repeated, rather than after acute, treatment. The findings also suggest that NOX inhibitors or agents suppressing oxidative stress may constitute a new area for research to understand how methamphetamine produces its deleterious and neurotoxic outcomes in the brain.
authors.affiliation: Department of Psychological Sciences, University of Missouri, Columbia, MO, USA; Bond Life Sciences Center, University of Missouri, Columbia, MO, USA. Electronic address: millerden@missouri.edu.
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Miller
authors.affiliation: Department of Psychological Sciences, University of Missouri, Columbia, MO, USA; Department of Statistics, University of Missouri, Columbia, MO, USA.
authors.forename: Clark E
authors.initials: CE
authors.lastname: Oelrichs
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, USA.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, USA.
authors.forename: Agnes
authors.initials: A
authors.lastname: Simonyi
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000188:drug therapy*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008694:Methamphetamine; C056165:acetovanillone; D004298:Dopamine
keywords: Apocynin; Behavior; Dopamine; Methamphetamine; Phenolic