Effects of anaesthetics on the loss of nigrostriatal dopaminergic neurons by 6-hydroxydopamine in rats.
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 microg 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 microg 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 microg 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.
Datla
K P
KP
Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, Charing Cross Campus, London, United Kingdom.
Zbarsky
V
V
Dexter
D T
DT
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018663:Adrenergic Agents / Q000633:toxicity*; D000704:Analysis of Variance; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006719:Homovanillic Acid / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009474:Neurons / Q000187:drug effects*; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018663:Adrenergic Agents; D000777:Anesthetics; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid