Increased striatal VMAT2 binding in mice after chronic administration of methcathinone and manganese

Brain Res. 2016 Dec 1:1652:97-102. doi: 10.1016/j.brainres.2016.09.034. Epub 2016 Sep 28.

Abstract

Intravenous use of a psychostimulant drug containing methcathinone (ephedrone) and manganese causes an irreversible extrapyramidal syndrome in drug abusers. We aimed to reproduce the syndrome in mice to evaluate dopaminergic damage. C57/B6 mice were intraperitoneally injected once a day with the study drug or saline for a period of 27 weeks. Motor activity was recorded in an automated motility-box. After 13 and 27 weeks of treatment, ex vivo digital autoradiography was performed using [11C]dihydrotetrabenazine ([11C]DTBZ). After 27 weeks of treatment [11C]DTBZ autoradiography demonstrated a significant increase in the striatum-to-cerebellum binding ratio compared with saline treated controls. At the same time point, there was no evident change in motor activity. Increased [11C]DTBZ binding may indicate vesicular monoamine transporter type 2 (VMAT2) function is altered. The lack of extrapyramidal symptoms in animals could be attributed to low dosing regimen or high metabolic rate.

Keywords: Ephedrone; Manganism; Methcathinone; PET; VMAT2.

MeSH terms

  • Animals
  • Autoradiography
  • Biomechanical Phenomena
  • Carbon Radioisotopes
  • Central Nervous System Stimulants / toxicity
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Gait / drug effects
  • Gait / physiology
  • Illicit Drugs / toxicity
  • Injections, Intraperitoneal
  • Male
  • Manganese / toxicity*
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Positron-Emission Tomography
  • Propiophenones / toxicity*
  • Psychotropic Drugs / toxicity*
  • Radiopharmaceuticals
  • Random Allocation
  • Substance-Related Disorders / diagnostic imaging
  • Substance-Related Disorders / metabolism*
  • Tetrabenazine / analogs & derivatives
  • Time Factors
  • Vesicular Monoamine Transport Proteins / metabolism*

Substances

  • Carbon Radioisotopes
  • Central Nervous System Stimulants
  • Illicit Drugs
  • Propiophenones
  • Psychotropic Drugs
  • Radiopharmaceuticals
  • Slc18a2 protein, mouse
  • Vesicular Monoamine Transport Proteins
  • dihydrotetrabenazine
  • monomethylpropion
  • Manganese
  • Tetrabenazine