Effects of benserazide-levodopa and donepezil on the dysfunction of motor behavior and cognitive working memory in long-term chronic cynomolgus monkey Parkinson’s disease model / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To evaluate the function of motor behavior and cognitive working memory of long-term Parkinson’s disease(PD) cynomolgus monkey, which has been seven years after induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) injection through internal carotid artery and investigate the effects of benserazide-levodopa and donepezil intervention on above mentioned dysfunction of motor behavior and cognitive working memory.Methods:Five long-term cynomolgus monkey PD models and five healthy ones with the same as normal control, behavioral evaluation was performed respectively, including Kurlan rating scale for evaluating the severity of PD symptoms, pick up test (PUT) for detecting the upper limb fine motor skills; physical activity monitoring(PAM) for analyzing the 24 h whole day locomotion exercise, and 12 h locomotion activity during sleep.In addition, delay matching-to-sample (DMTS) for detecting cognitive working memory.Furthermore, benserazide-levodopa was administered orally for 10 days, twice a day, 250 mg each time, and after 10 days interval, and donepezil was orally administered for 14 days, once a day, 5 mg each time, and all above behavioral indicators were tested after madopar and donepezil intervention respectively.Results:Kurlan score (4.10±1.01) in the long-term chronic PD model group was significantly increased than that in the normal control (0) ( P<0.01). Compared with the normal control, PUT test for retrieving the food items was not able to be performed with the right upper limb( P<0.01). The time for picking up the food items in left upper limbs ((23.14±7.96)s) was no significant difference from that in normal control group ((12.52±2.71)s) ( P>0.05). The 24 h total locomotion (2 3531.75±9 065.85) was not different from that normal control group (52 750.34±27 598.89) ( P>0.05). The 12 h total locomotor activity during sleep period (2 911.34±1 845.47) was not different from the normal control group (3 310.67±1 721.63). The DMTS correction rate in long-term chronic PD group at 5 s, 10 s, 15 s, and 30 s delay were (61.60±9.21)%, (51.20±11.80)%, (49.60±8.29)%, (60.80±4.38)%, respectively, and was significantly decreased ( P<0.01, P<0.05, P<0.01, P<0.01) compared with those in normal control group ((96.80±3.35)%, (84.80±8.67)%, (80.80±7.69)%, (74.40±4.56)%, respectively). After intervention of benserazide-levodopa, there was no significant difference in Kurlan score (2.60±0.38) compared with that before intervention (4.10±1.01) ( P>0.05); the PUT test in right upper limb was still not able to be performed, the time for retrieving the food items in left upper limb ((15.40±4.14)s) was less than that before administration ((23.14±7.96)s) ( P<0.05); the 24 h total locomotion activity (44 128.25±16 464.71) was increasesd than that before intervention (23 531.75±9 065.85) ( P<0.05). There was no significant difference in 12 h locomotion activity during sleep (4 931.84±2 304.06) compared with that before madopar administration (2 911.34±1 845.47) ( P>0.05). There was no significant difference between the DMTS correction rate at 5 s, 10 s, 15 s, 30 s before and after madopar intervention(all P>0.05). There was no difference in all behavioral indicators (all P>0.05) between before and sfter donepezil administration. Conclusion:Long-term chronic PD monkeys still exist symptoms and motor behavior and cognitive working memory impairment.The benserazide-levodopa intervention can improve the motor behavior and cognitive working memory dysfunction, indicating that the lesion of functional integrity of dopaminergic system is still exist in long-term chronic Parkinsonian monkeys.Donepezil intervention is not able to reverse the motor and cognitive working memory, implying that mechanism underlying the cognitive memory impairment of PD monkeys is different from that in Alzheimer's disease.