Exercise effects on motor and affective behavior and catecholamine neurochemistry in the MPTP-lesioned mouse

This study used 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) in mice to determine if exercise improves behavior and dopamine (DA) and serotonin (5HT) content. Male C57BL/6 mice received MPTP (4 x 20 mg/kg) or saline. They remained sedentary or exercised by treadmill or voluntary running wheel for 6 weeks (n = 8/group). Saline-treated mice ran significantly faster on running wheels (22.8 +/- 1.0 m/min) than on treadmill (8.5 +/- 0.5 m/min), and MPTP lesion did not reduce voluntary exercise (19.3 +/- 1.5 m/min, p > 0.05). There was a significant effect of both lesion and exercise on overall Rotarod performance (ORP): MPTP lesion reduced ORP, while treadmill exercise increased ORP vs sedentary mice (p < 0.05). MPTP increased anxiety in the marble-burying test: sedentary lesioned mice buried more marbles (74.0 +/- 5.2%) than sedentary controls (34.8 +/- 11.8%, p < 0.05). Conversely, exercise reduced anxiety on the elevated plus maze. Among saline-treated mice, those exposed to voluntary wheel-running showed an increased percent of open arm entries (49.8 +/- 3.5%, p < 0.05) relative to sedentary controls (36.2 +/- 4.0%, p < 0.05). Neither MPTP nor exercise altered symptoms of depression measured by sucrose preference or tail suspension. MPTP significantly reduced DA in striatum (in sedentary lesioned mice to 42.1 +/- 3.0% of saline controls), and lowered 5HT in amygdala and striatum (in sedentary lesioned mice to 86.1 +/- 4.1% and 66.5 +/- 8.2% of saline controls, respectively); exercise had no effect. Thus, exercise improves behavior in a model of DA depletion, without changes in DA or 5HT. (C) 2010 Elsevier B.V. All rights reserved.