Article

Behavior, neurotransmitters and inflammation in three regimens of the MPTP mouse model of Parkinson’s disease

Department of Biomedical Sciences, AVC, University of Prince Edward Island, and NRC Institute for Nutriscience and Health, Charlottetown, PE, Canada C1A 5T1.
Physiology & Behavior (Impact Factor: 3.03). 06/2009; 98(1-2):130-8. DOI: 10.1016/j.physbeh.2009.04.021
Source: PubMed

ABSTRACT Three common dosing regimens of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model of Parkinson's disease (PD) were compared in C57BL/6 mice on behavior, striatal and extra-striatal neurotransmission, and brain cytokines, to clarify the differences between regimens on these variables. Acute regimen: Rotorod performance and open field grooming were decreased. Striatal dopamine (DA) was depleted, but DA turnover increased. Striatal noradrenalin (NA), frontal cortex serotonin (5-HT) and midbrain NA and DA were all depleted. Sub-acute regimen: Opposite to the acute regimen, rotorod and pole test performance, and open field grooming were all increased. Striatal DA was depleted, but DA turnover was increased more than in the acute regimen. Striatal 5-HT turnover and cortical NA were increased as well. Chronic regimen: Rotorod performance was impaired, but open field distance moved increased. Striatal DA was severely depleted and DA and 5-HT turnover strongly increased. Striatal 5-HT, frontal cortex NA and DA, and cortical DA were all depleted. Pro-inflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-10 were only increased in the chronic regimen, but these cytokines were found to be similarly related to striatal DA turnover in all regimens. The study demonstrated that the presence of behavioral differences between regimens may depend on the type of behavioral tests used and the extent to which dopaminergic, non-dopaminergic and extra-striatal neurotransmission are affected in the regimens. The study also provided additional evidence for the validity of the relatively new chronic MPTP/probenecid model. In all, the results suggested that dosing regimens should be carefully pre-considered.

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    • "sion and motor behavior is further supported by the study of the MPTP - intoxicated mice . Indeed , in intoxicated mice 10 days after intoxication , the only change in motor behavior was a spontaneous hyperactivity . Deficits in motor behavior have frequently been reported in MPTP - intoxicated mice ( Sedelis et al . 2001 ; Meredith et al . 2008 ; Luchtmann et al . 2009 ) , but only when the evaluations were performed 1 – 5 days after intoxication . After 1 week , this acute motor deficit was reported to be attenuated and a spontaneous hyperactivity was observed even after chronic MPTP intoxication ( Rouss - elet et al . 2003 ; Meredith and Kang 2006 ) . The late spontaneous hyperactivity observed in c"
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