Ellagic acid improves hyperalgesia and cognitive deficiency in 6-hydroxidopamine induced rat model of Parkinson's disease

Iran J Basic Med Sci. 2015 Jan;18(1):38-46.


Objectives: 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 6-hydroxidopamine (6-OHDA).

Materials and methods: Right medial forebrain bundle (MFB) was lesioned by injecting 6-OHDA (16 µg/2 µl), in PD-animals. Sham operated animals received vehicle instead of 6-OHDA. PD was approved by apomorphine-induced contralateral rotation. EA (50 mg/kg/2 ml, PO, for 10 days) was administered to PD-EA group. Some PD-animals received pramipexole (PPX; 2 mg/kg/2 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: 6-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: 6-OHDA; Cognition; Ellagic acid; Pain; Parkinson’s disease; Rat.