Severity assessment in the unilateral and bilateral 6-OHDA rat Parkinson model: Telemetric monitoring of heart rate and activity

In animal experimentation, welfare and severity assessments are necessary to meet legal and ethical requirements. Injection of 6-hydroxydopamine (6-OHDA) into the nigrostriatal system of rats is used as a model for Parkinson's disease (PD). Unilateral intranigral infusion of 6-OHDA leads to a massive destruction of nigrostriatal dopaminergic neurons and concomitant motor disturbances. After injection of Levodopa (L-Dopa), these rats develop dyskinesias. The bilateral model leads to slow and incomplete retrograde degeneration of dopaminergic neurons. For severity assessment, we quantitatively measured weight, heart rate and activity.In rats (n=16), a telemetric device was subcutaneously implanted. After recovery, rats received either unilateral stereotaxic injection of 6-OHDA into the substantia nigra (n=8) or bilateral into the striatum (n=8). After unilateral injection, rats were subcutaneously injected with L-Dopa (10 mg/kg) for 21 days. Perioperatively and during L-Dopa we measured weight, heart rate and activity during the first two hours after light on and off, as well as directly before and after L-Dopa injection.Bilateral injection led to weight loss for the first four postoperative days (two rats nearly 20%; p<0.05), unilateral injection had no effect. Heart rate was enhanced for three days in both models, activity measures were not affected. L-Dopa had no effect on weight and heart rate, but enhanced activity.This indicates that perioperatively rats` wellbeing is more affected by bilateral injection with incomplete loss of nigral dopamine, although heart rate measures also indicate disturbed wellbeing after unilateral injection. The development of dyskinesias has only mild and transient effects on rat`s wellbeing.