Effects of Treadmill Exercise on Dopaminergic Transmission in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Mouse Model of Basal Ganglia Injury

Abstract

Studies have suggested that there are beneficial effects of exercise in patients with Parkinson's disease, but the underlying molecular mechanisms responsible for these effects are poorly understood. Studies in rodent models provide a means to examine the effects of exercise on dopaminergic neurotransmission. Using intensive treadmill exercise, we determined changes in striatal dopamine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse. C57BL/6J mice were divided into four groups: (1) saline, (2) saline plus exercise, (3) MPTP, and (4) MPTP plus exercise. Exercise was started 5 d after MPTP lesioning and continued for 28 d. Treadmill running improved motor velocity in both exercise groups. All exercised animals also showed increased latency to fall (improved balance) using the accelerating rotarod compared with nonexercised mice. Using HPLC, we found no difference in striatal dopamine tissue levels between MPTP plus exercise compared with MPTP mice. There was an increase detected in saline plus exercise mice. Analyses using fast-scan cyclic voltammetry showed increased stimulus-evoked release and a decrease in decay of dopamine in the dorsal striatum of MPTP plus exercise mice only. Immunohistochemical staining analysis of striatal tyrosine hydroxylase and dopamine transporter proteins showed decreased expression in MPTP plus exercise mice compared with MPTP mice. There were no differences in mRNA transcript expression in midbrain dopaminergic neurons between these two groups. However, there was diminished transcript expression in saline plus exercise compared with saline mice. Our findings suggest that the benefits of treadmill exercise on motor performance may be accompanied by changes in dopaminergic neurotransmission that are different in the injured (MPTP-lesioned) compared with the noninjured (saline) nigrostriatal system.

Nociceptin/orphanin FQ receptor blockade attenuates MPTP-induced parkinsonism

“…Nevertheless, we found that mice displayed increased immobility time (likely reflecting increased akinesia), reduced number of steps (possibly reflecting increased akinesia, bradykinesia and rigidity) and overall impaired motor performance (possibly reflecting loss of coordination and overall gait ability) at 7 days after MPTP intoxication. These data are consistent with that reported by other authors using the bar (Kato et al, 2004;Watanabe et al, 2008) and the treadmill (Petzinger et al, 2007) test at 7 days after MPTP administration (4 × 20 mg/kg). In the same study, no differences in rotarod performance after MPTP intoxication were observed.…”

The Effect of Exercise Training in Improving Motor Performance and Corticomotor Excitability in People With Early Parkinson's Disease

“…Animal models of PD have also supported activity-dependent neuroplasticity after intensive treadmill training as measured through changes in dopamine handling and neurotransmission, including increased dopamine release, decreased uptake and an increase in the postsynaptic dopamine D2-receptor subtype within the basal ganglia. 2,60 …”

Aerobic exercise decreases the positive-reinforcing effects of cocaine

“…Several pieces of evidence suggest that acute bouts of exercise produce effects that are neurochemically similar to those produced by cocaine and other psychomotor stimulants. For instance, like cocaine, exercise increases central dopamine concentrations (Heyes et al, 1988;Hattori et al, 1994;Meeusen et al, 1997;Petzinger et al, 2007), and these increases are positively correlated with exercise output (Freed and Yamamoto, 1985). Importantly, chronic, long-term exercise leads to sustained increases in dopamine concentrations (Bauer et al, 1989) and compensatory changes in dopamine binding proteins (Fisher et al, 2004).…”

“…For instance, acute bouts of exercise increase central dopamine concentrations (Heyes et al, 1988;Hattori et al, 1994;Meeusen et al, 1997;Petzinger et al, 2007), and chronic exercise leads to sustained increases in dopamine concentrations and compensatory alterations in dopamine binding proteins (Gilliam et al, 1984;MacRae et al, 1987;Fisher et al, 2004). Given that many addictive drugs produce their positive-reinforcing effects by increasing dopamine transmission in mesolimbic and mesocortical pathways (Goeders and Smith, 1983;Caine and Koob, 1994;Wise et al, 1995;Pich et al, 1997), chronic exercise may produce functional changes in these pathways that leave an organism less susceptible to their positive-reinforcing effects.…”