Long lasting behavioural effects on cuprizone fed mice after neurotoxicant withdrawal

Behav Brain Res. 2019 May 2;363:38-44. doi: 10.1016/j.bbr.2019.01.036. Epub 2019 Jan 28.


Destruction of the myelin sheath in the central nervous system (CNS) is prominent in many clinico-pathologic conditions. Among animal models that reproduce the pathological features of de- and remyelination processes, the mouse model of cuprizone administration is widely used. Both hyperactivity and motor impairment have been reported upon cuprizone exposure. The aim of the present study was to assess behaviour in mice after CPZ withdrawal.To summarize, animals showed hypo-activity and deficits in motor coordination when they were subjected to acute demyelinating insult while minor exploratory activity, impairment in motor coordination and lower anxiety levels emerged when remyelination was reached following cuprizone withdrawal. A recovery period of 6 weeks after removal of CPZ was not accompanied by a similar return of normal activity indicating long lasting behavioural effects caused by this neurotoxicant. Specifically, the recovery group showed impairments in neurological functions involved in sensorimotor, neuromuscular, motor coordination and the capacity to cope with a stress-inducing event.

Keywords: Cuprizone; Demyelination; Motor coordination and anxiety; Neurobehavioral screening; Remyelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Central Nervous System / drug effects
  • Cuprizone / adverse effects*
  • Cuprizone / pharmacology*
  • Demyelinating Diseases / metabolism
  • Disease Models, Animal
  • Grooming / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Skills / drug effects
  • Myelin Sheath / pathology
  • Oligodendroglia / drug effects


  • Cuprizone