title: Nest building performance following MPTP toxicity in mice.
abstract: Systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice is one of the primary models used to evaluate neuroprotective and symptomatic treatment strategies for Parkinson's disease. Many behavioral methods for evaluation of MPTP toxicity have been described, but they often involve challenging scenarios that require handling and transfer of animals to novel environments and in some cases prior animal training. These factors can profoundly influence animal behavior and potentially influence experimental outcome. Presented here is a new nest building scoring paradigm based on the animals' normal home cage behavior that is a simple, non-invasive, and reproducible measure for estimating neurological dysfunction in MPTP intoxicated mice. Nest building behavior requires orofacial and forelimb movement and has been shown to be dopamine-dependent making it a possible method for assessing parkinsonian-like symptoms. Significant deficits in nest building scores after 2x20 and 2x25 mg/kg MPTP coincided with a 90% reduction in striatal dopamine. Nest building deficits could be detected for more than a week after intoxication. However, after 28 days the change in behavior was no longer detected, which may reflect the plasticity of the tyrosine hydroxylase positive neurons in the dorsolateral part of striatum.
authors.affiliation: H Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. TSA@lundbeck.com
authors.forename: Thomas Nikolaj
authors.initials: TN
authors.lastname: Sager
authors.forename: Jeppe
authors.initials: J
authors.lastname: Kirchhoff
authors.forename: Arne
authors.initials: A
authors.lastname: Mørk
authors.forename: Johan
authors.initials: J
authors.lastname: Van Beek
authors.forename: Kenneth
authors.initials: K
authors.lastname: Thirstrup
authors.forename: Michael
authors.initials: M
authors.lastname: Didriksen
authors.forename: Jes Brix
authors.initials: JB
authors.lastname: Lauridsen
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020267:MPTP Poisoning / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009425:Nesting Behavior / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity; D020127:Recovery of Function / Q000502:physiology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D009498:Neurotoxins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase