Ellagic acid improves hyperalgesia and cognitive deficiency in ۶-hydroxidopamine induced rat model of Parkinson’s disease

Objective(s):Parkinson's disease (PD) is known for motor impairments. But often, there are non-motor symptoms such as cognitive deficiency and pain misperception, owing to possible role of nigrostriatal pathway. Antioxidants have protective effect on free radical-induced neuronal damage in PD. To further address, we examined the effects of ellagic acid (EA) in a rat model of PD induced by ۶-hydroxidopamine (۶-OHDA). Materials and Methods: Right medial forebrain bundle (MFB) was lesioned by injecting ۶-OHDA (۱۶ µg/۲ µl), in PD–animals.Sham operated animals received vehicle instead of ۶-OHDA. PD was approved by apomorphine-induced contralateral rotation. EA (۵۰ mg/kg/۲ ml, PO, for ۱۰ days) was administered to PD-EA group. Some PD-animals received pramipexole (PPX; ۲ mg/kg/۲ ml, PO) as a positive control group. Analgesia was measured by tail-flick and hot-plate tests. Passive avoidance task was measured by shuttle box apparatus to record the initial and step-through latency. Spatial cognition task was evaluated by Morris water maze test, measuring the escape latency time, path length, swimming speed and time spent in target quadrant. Results: MFB-lesioned rats showed hyperalgesic responses to the stimulus in tail-flick and hot-plate tests. Also they showed memory and learning deficit in cognitive tests. These effects reversed by EA treatment. Conclusion: ۶-OHDA can induce oxidative stress and can disrupt the neural mechanisms underlying proper integration of painful stimuli and cognitive processes in MFB-lesioned rats. Consequently, nigrostriatal pathway can play possible role in nociception and cognition. EA, a natural antioxidant, has neuroprotective effect on this pathway and can ameliorate this defect and be considered in PD management.

Keywords:

۶-OHDA , Cognition , Ellagic acid , Pain , Parkinson's disease , Rat