Long lasting behavioural effects on cuprizone fed mice after neurotoxicant withdrawal

Abstract

HighlightsDemyelinated animals showed less grooming activity and worse motor coordination.At 6 weeks, CPZ‐fed animals showed impairments in sensorimotor and exploratory behaviour.Animals undergoing remyelination displayed less rearings, worse motor coordination, gait abnormalities and anxiety.At 10 weeks, CPZ‐fed mice displayed worse limb coordination and an anxiogenic response.Recovered mice showed dysfunctions in sensorimotor, neuromuscular, motor coordination and coping with a stress event. &NA; 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.