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Blockade of m1 muscarinic acetylcholine receptors modulates the methamphetamine-induced psychomotor stimulant effect

Academic Article
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Overview

authors

  • Lee, K. W.
  • Tian, Y. H.
  • You, I. J.
  • Kwon, S. H.
  • Ha, R. R.
  • Lee, S. Y.
  • Kim, H. C.
  • Jang, Choon-Gon

publication date

  • June 2008

journal

  • Neuroscience  Journal

abstract

  • Muscarinic acetylcholine receptors (M1-M5) regulate many key functions of the CNS and peripheral nervous system. In the present study, the role of M1 muscarinic receptors (M1R) in the psychomotor stimulant and sensitizing properties of methamphetamine (METH) is investigated using molecular, neurochemical, and behavioral approaches. Acute and repeated treatment with METH increased M1R mRNA expression in the frontal cortex and the CA2 region of the hippocampus. Repeated treatment with METH also increased M1R mRNA expression in the dentate gyrus. Dicyclomine, an M1R antagonist, did not affect the psychomotor effect of METH, but it attenuated METH-induced increases in the dopamine (DA) efflux in the nucleus accumbens (NAc). Dicyclomine enhanced the psychomotor effect of METH after repeated treatment with METH and 8.0 mg/kg of dicyclomine, and also augmented the increase in the NAc DA overflow evoked by repeated METH treatment. These results suggest that M1R plays a role in the METH-induced psychomotor stimulant effect by changing the release of DA in the NAc of mice.

subject areas

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Brain
  • Central Nervous System Stimulants
  • Dicyclomine
  • Dopamine
  • Drug Interactions
  • Male
  • Methamphetamine
  • Mice
  • Mice, Inbred ICR
  • Motor Activity
  • Muscarinic Antagonists
  • Psychomotor Agitation
  • RNA, Messenger
  • Receptor, Muscarinic M1
  • Time Factors
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Research

keywords

  • dicyclomine
  • dopamine release
  • locomotor activity
  • microdialysis
  • nucleus accumbens
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Identity

International Standard Serial Number (ISSN)

  • 0306-4522

Digital Object Identifier (DOI)

  • 10.1016/j.neuroscience.2008.02.021

PubMed ID

  • 18455881
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Additional Document Info

start page

  • 1235

end page

  • 1244

volume

  • 153

issue

  • 4

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