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Chronic wheel running reduces maladaptive patterns of methamphetamine intake: Regulation by attenuation of methamphetamine-induced neuronal nitric oxide synthase

Academic Article
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Overview

authors

  • Engelmann, A. J.
  • Aparicio, M. B.
  • Kim, A.
  • Sobieraj, J. C.
  • Yuan, C. J.
  • Grant, Y.
  • Mandyam, Chitra

publication date

  • March 2014

journal

  • Brain Structure & Function  Journal

abstract

  • We investigated whether prior exposure to chronic wheel running (WR) alters maladaptive patterns of excessive and escalating methamphetamine intake under extended access conditions, and intravenous methamphetamine self-administration-induced neurotoxicity. Adult rats were given access to WR or no wheel (sedentary) in their home cage for 6 weeks. A set of WR rats were injected with 5-bromo-2'-deoxyuridine (BrdU) to determine WR-induced changes in proliferation (2-h old) and survival (28-day old) of hippocampal progenitors. Another set of WR rats were withdrawn (WRw) or continued (WRc) to have access to running wheels in their home cages during self-administration days. Following self-administration [6 h/day], rats were tested on the progressive ratio (PR) schedule. Following PR, BrdU was injected to determine levels of proliferating progenitors (2-h old). WRc rats self-administered significantly less methamphetamine than sedentary rats during acquisition and escalation sessions, and demonstrated reduced motivation for methamphetamine seeking. Methamphetamine reduced daily running activity of WRc rats compared with that of pre-methamphetamine days. WRw rats self-administered significantly more methamphetamine than sedentary rats during acquisition, an effect that was not observed during escalation and PR sessions. WR-induced beneficial effects on methamphetamine self-administration were not attributable to neuroplasticity effects in the hippocampus and medial prefrontal cortex, but were attributable to WR-induced inhibition of methamphetamine-induced increases in the number of neuronal nitric oxide synthase expressing neurons and apoptosis in the nucleus accumbens shell. Our results demonstrate that WR prevents methamphetamine-induced damage to forebrain neurons to provide a beneficial effect on drug-taking behavior. Importantly, WR-induced neuroprotective effects are transient and continued WR activity is necessary to prevent compulsive methamphetamine intake.
  • We investigated whether prior exposure to chronic wheel running (WR) alters maladaptive patterns of excessive and escalating methamphetamine intake under extended access conditions, and intravenous methamphetamine self-administration-induced neurotoxicity. Adult rats were given access to WR or no wheel (sedentary) in their home cage for 6�weeks. A set of WR rats were injected with 5-bromo-2'-deoxyuridine (BrdU) to determine WR-induced changes in proliferation (2-h old) and survival (28-day old) of hippocampal progenitors. Another set of WR rats were withdrawn (WRw) or continued (WRc) to have access to running wheels in their home cages during self-administration days. Following self-administration [6�h/day], rats were tested on the progressive ratio (PR) schedule. Following PR, BrdU was injected to determine levels of proliferating progenitors (2-h old). WRc rats self-administered significantly less methamphetamine than sedentary rats during acquisition and escalation sessions, and demonstrated reduced motivation for methamphetamine seeking. Methamphetamine reduced daily running activity of WRc rats compared with that of pre-methamphetamine days. WRw rats self-administered significantly more methamphetamine than sedentary rats during acquisition, an effect that was not observed during escalation and PR sessions. WR-induced beneficial effects on methamphetamine self-administration were not attributable to neuroplasticity effects in the hippocampus and medial prefrontal cortex, but were attributable to WR-induced inhibition of methamphetamine-induced increases in the number of neuronal nitric oxide synthase expressing neurons and apoptosis in the nucleus accumbens shell. Our results demonstrate that WR prevents methamphetamine-induced damage to forebrain neurons to provide a beneficial effect on drug-taking behavior. Importantly, WR-induced neuroprotective effects are transient and continued WR activity is necessary to prevent compulsive methamphetamine intake.

subject areas

  • Analysis of Variance
  • Animals
  • Bromodeoxyuridine
  • Caspase 3
  • Cell Proliferation
  • Central Nervous System Stimulants
  • Disease Models, Animal
  • Hippocampus
  • Ki-67 Antigen
  • Male
  • Methamphetamine
  • Neural Stem Cells
  • Neurons
  • Neurotoxicity Syndromes
  • Nitric Oxide Synthase
  • Oncogene Proteins v-fos
  • Rats
  • Rats, Wistar
  • Reward
  • Running
  • Self Administration
  • Time Factors
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Research

keywords

  • AC-3
  • BrdU
  • Hippocampus
  • Ki-67
  • Medial prefrontal cortex
  • Self-administration
  • Subgranular zone
  • nNOS
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Identity

PubMed Central ID

  • PMC3702684

International Standard Serial Number (ISSN)

  • 1863-2661 (Electronic) 1863-2653 (Linking)

Digital Object Identifier (DOI)

  • 10.1007/s00429-013-0525-7

PubMed ID

  • 23443965
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Additional Document Info

start page

  • 657

end page

  • 672

volume

  • 219

issue

  • 2

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