Effects of anaesthetics on the loss of nigrostriatal dopaminergic neurons by 6-hydroxydopamine in rats

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Various studies use ketamine/xylazine, fentanyl/medetomidine, etorphine/methotrimeprazine, and isoflurane anaesthesia for creating the 6-hydroxydopamine (6-OHDA)-lesion rat model of Parkinson's disease. As these anaesthetics are known to modulate uptake and turnover of dopamine and that 6-OHDA-induced neurotoxicity is also dependents on uptake/turnover, we studied the effects of these anaesthetics on the extent of nigrostriatal dopaminergic damage caused by 6-OHDA. Infusion of 8 μg of 6-OHDA into the medial forebrain bundle significantly reduced the numbers of dopaminergic cells in nigra and striatal concentrations of dopamine in animals anaesthetized with fentanyl/medetomidine, etorphine/methotrimeprazine and isoflurane but not with ketamine/xylazine. In the latter group, however, increasing the dose of 6-OHDA to 10 and 12 μg resulted in a moderate (15 and 29%), but significant loss of dopaminergic cells. A severe loss of dopaminergic cells (59% and 81%) was seen with these doses in isoflurane-anaesthetized animals, but with only 8 μg in etorphine/methotrimeprazine-anaesthetized animals. Thus, these results suggest that the extent of nigrostriatal dopaminergic neuronal loss with 6-OHDA seems to be influenced by anaesthetic used during the surgery.

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