Ketamine anaesthesia interferes with the quinolinic acid-induced lesion in a rat model of Huntington's disease

Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, is a commonly used injectable anaesthetic agent. In the present study, ketamine- and isoflurane-induced anaesthesias were tested to identify the influence of different anaesthesia methods in conjunction with the unilateral quinolinic acid-induced excitotoxic lesion rat model of Huntington's disease (HD). Quinolinic acid, a glutamate analogue, exerts its excitotoxic effect via the NMDA receptor, the principle target of ketamine as well, rendering the choice of anaesthesia an important pharmacokinetic issue. Twenty Sprague-Dawley females were lesioned using quinolinic acid: one group was anaesthetised with ketamine and the other with isoflurane. The injection coordinates and the dosage of quinolinic acid were identical. Two weeks post-lesion, the animals were tested on apomorphine-induced rotation test, followed by perfusion, immunohistochemical and volumetric analysis. The isoflurane, compared with the ketamine, anaesthetised animals showed greater ipsilateral rotation behaviour, larger striatal lesions and significant differences in other measurements reflecting the extent of the lesion. The data demonstrates that the use of ketamine anaesthesia in the excitotoxic model of HID can severely compromise the development of the lesion. (C) 2009 Elsevier B.V. All rights reserved.