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

Abstract

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 20mg/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+/-1.0m/min) than on treadmill (8.5+/-0.5m/min), and MPTP lesion did not reduce voluntary exercise (19.3+/-1.5m/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.

Figure 1

Top: Body weights (mean±SEM) in MPTP- (left, filled symbols) and saline-treated (NaCl) mice (right, open symbols) before lesion (Week 0) and at the end of the study (Week 6). Bottom: Exercise velocity (m/min) and distance (m/day) in mice subject to forced treadmill exercise (squares) and in MPTP- and saline-treated mice exercising voluntarily on running wheels (triangles). Exercise effects are denoted by letters (MPTP: a, b; saline: x, y); bars with common letters in the same lesion group are not different. * identifies differences between MPTP- and saline-treated mice in the same exercise group.

Figure 2

Top: Latency to fall (in seconds) from Rotarod spindle at increasing speeds (12–26 rpm) in MPTP- (filled symbols) and saline-treated mice (NaCl, open symbols). Asterisks indicate significant difference between NaCL and MPTP-lesioned mice. Bottom: Overall Rotarod performance (ORP) in MPTP (left) or NaCl unlesioned mice (right), and in mice undergoing forced treadmill exercise (open bars), voluntary wheel running exercise (grey bars) or that were sedentary (filled bars). By 2-factor ANOVA, § indicates effect of lesion, † indicates effect of exercise. In post-hoc analyses, exercise effects are denoted by letters (MPTP: a, b; saline: x, y); bars with common letters in the same lesion group are not different.

Figure 3

Top: Percent of marbles buried (mean±SEM) in MPTP- (left) and saline-treated mice (right) that were exercised on a treadmill (open bars) or running wheel (grey bars) or that remained sedentary (filled bars). Bottom: Percent of open arm entries on the elevated plus maze. By 2-factor ANOVA, § indicates effect of lesion, † indicates effect of exercise. In post-hoc analyses, exercise effects are denoted by letters (MPTP: a, b; saline: x, y); bars with common letters in the same lesion group are not different. * identifies differences between MPTP- and saline-treated mice in the same exercise group.

Figure 4

Top: Percent sucrose preference (mean±SEM) measured weekly in MPTP- (left) and saline-treated mice (right) that were exercised on a treadmill (open bars) or running wheel (grey bars) or that remained sedentary (filled bars). Bottom: Percent immobility during tail suspension. There was no effect of lesion or exercise in either test of depression. Exercise effects are denoted by letters (MPTP: a, b; saline: x, y); bars with common letters in the same lesion group are not different.

Figure 5

Top: Serum corticosterone concentrations (mean±SEM) in MPTP- (left) and saline-treated mice (right) that were exercised on a treadmill (open bars) or running wheel (grey bars) or that remained sedentary (filled bars). Bottom: Thymus weights. By 2-factor ANOVA, § indicates effect of lesion. In post-hoc analyses, exercise effects are denoted by letters (MPTP: a, b; saline: x, y); bars with common letters in the same lesion group are not different. * identifies differences between MPTP- and saline-treated mice in the same exercise group.

Figure 6

DA levels in four brain regions expressed as percent of saline-treated sedentary controls (mean±SEM) in MPTP- (left) and saline-treated mice (right) that were exercised on a treadmill (open bars) or running wheel (grey bars) or that remained sedentary (filled bars). By 2-factor ANOVA, § indicates effect of lesion. In post-hoc analyses, exercise effects are denoted by letters (MPTP: a, b; saline: x, y); bars with common letters in the same lesion group are not different. * identifies differences between MPTP- and saline-treated mice in the same exercise group.

Figure 7

5HT levels in four brain regions expressed as percent of saline-treated sedentary controls (mean±SEM) in MPTP- (left) and saline-treated mice (right) that were exercised on a treadmill (open bars) or running wheel (grey bars) or that remained sedentary (filled bars). By 2-factor ANOVA, § indicates effect of lesion. In post-hoc analyses, exercise effects are denoted by letters (MPTP: a, b; saline: x, y); bars with common letters in the same lesion group are not different. * identifies differences between MPTP- and saline-treated mice in the same exercise group.