Voluntary Running Provides Neuroprotection in Rats After 6-Hydroxydopamine Injection into the Medial Forebrain Bundle

Abstract

Neurotoxic drugs such as 6-hydroxydopamine (6-OHDA) have been used to mimic a Parkinsonian state in a rat model. The toxic effect of 6-OHDA has been shown to be reduced in rats that were forced to use the impaired limb immediately after unilateral 6-OHDA injection. The aim of this study was to determine whether dopamine neurons in the substantia nigra are spared in rats that exercise voluntary. Two groups of rats were placed in cages with attached running wheels 7 days prior to injection of 6-OHDA (10 microg/4 microL saline) into the medial forebrain bundle. The running wheels of the control group were immobilized for the duration of the study. After 6-OHDA injection, the rats were returned to their respective cages where they remained for a further period of 14 days. Wheel revolutions during free running were recorded daily in the experimental group. At the end of this period the rats were injected with apomorphine (0.5 mg/kg, s.c.) and the number and direction of rotations was recorded. Rats that exercised in the running wheels did not rotate contralaterally in response to apomorphine injection, suggesting that dopamine neurons had been spared sufficiently from the toxic effects of 6-OHDA injection to prevent upregulation of postsynaptic dopamine receptors in the striatum.

Continuous and Intermittent Nicotine Treatment Reduces l-3,4-Dihydroxyphenylalanine (l-DOPA)-Induced Dyskinesias in a Rat Model of Parkinson's Disease

“…Several approaches were used to evaluate the effect of nicotine treatment on motor function in rats with a unilateral nigrostriatal lesion. One of these involved measurement of dopaminergic drug-induced rotational behavior using a computerized system (ROTOMAX, AccuScan System; AccuScan Instruments, Inc.) (Mabandla et al, 2004;Howells et al, 2005;Steiner et al, 2006;Lindgren et al, 2007). This test has been extensively used for 6-OHDA-lesioned rats because it is objective, reliable, and provides a good index of dopaminergic denervation (Meredith and Kang, 2006).…”

Driving GDNF expression: The green and the red traffic lights

“…Sparing of dopaminergic neurons from toxin action, assessed by measuring dopamine, its metabolites and transporters in the striatum, or THpositive cells in the substantia nigra, strongly supports a neuroprotective role for physical exercise. These studies raised the hypothesis ) that up-regulation of GDNF might mediate, or at least contribute to, the protection of the nigrostriatal pathway, and the improvement of motor function observed in many studies of forced limb use or running-wheel exercise in both the 6-OHDA (Mabandla et al, 2004;Tillerson et al, 2001Tillerson et al, , 2003 and the MPTP (Fisher et al, 2004;Tillerson et al, 2003) models of PD. However, exercise of the affected limb is protective only when initiated in a time window after toxic injury.…”

Limb use and complex ultrasonic vocalization in a rat model of Parkinson's disease: Deficit-targeted training

“…Non-specific exercise in rodents, such as voluntary and treadmill running, has been associated with neurogenesis [17], angiogenesis [18], increased neurotrophic factors [19] and increased levels of dopamine [20]. However, although behavioural and/or neural outcomes were found to be improved with running wheel or treadmill activity [10,19,21], beneficial effects on specific skilled behaviour have not been demonstrated [20]. Thus, it appears that early interventions might be administered more effectively with task-specific targeted skill training.…”