Behavioral deficits in the cuprizone-induced murine model of demyelination/remyelination.
The neurotoxicant cuprizone has been used extensively to create a mouse model of demyelination. However, the effects on behavior of cuprizone treatment have not been previously reported. We have analyzed the behavioral changes of mice given a diet containing 0.2% cuprizone for 6 weeks followed by 6 weeks of recovery. Behavior was assessed using a range of tests: the functional observation battery, the open-field test and the rota-rod test. Concurrent with the start of demyelination, at 3 and 4 weeks of 0.2% cuprizone treatment, the animals exhibited an increase in central nervous system activity and an inhibited anxiogenic response to the novelty challenge test. At 5 weeks of treatment (the period of maximal demyelination) equilibrium was altered and sensorimotor reactivity was also affected. Further, rota-rod analysis demonstrated that the treated group had poorer motor co-ordination than control animals. This effect was not reversed 6 weeks after cuprizone withdrawal. The animals in the recovery period also exhibited difficulties in the rota-rod progressive learning task. Our results indicate that behavioral deficits follow the course of demyelination-remyelination induced by administration of 0.2% cuprizone, and that some of the changes persist even after 6 weeks on normal diet.
Franco-Pons
Neus
N
Unitat de Psiquiatria i Psicologia Mèdica, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, C/Sant Llorenç 21, 43201 Reus, Spain.
Torrente
Margarita
M
Colomina
Maria Teresa
MT
Vilella
Elisabet
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000378:metabolism*
D004676:Myelin Basic Protein; D003471:Cuprizone