Meeting Abstract
25.4 Friday, Jan. 4 MK-801 Induces Arousal From Hibernation Through Peripheral Effects JINKA, TULASI**; DREW, KELLY; TOIEN, OIVIND; RASLEY, BRIAN; Institute of Arctic Biology; Institute of Arctic Biology; Institute of Arctic Biology; Chemistry and Biochemistry fttrj@uaf.edu
Arctic ground squirrels (AGS, Spermophilus parryii ) hibernate and metabolic suppression seen in hibernation has implications for ischemia tolerance. N-methyl-D-aspartate (NMDA) type glutamate receptors are thought to play a regulatory role in maintenance of torpor in hibernation, and respiratory control (Harris and Milsom,2000).The purpose of the present study was to test the hypothesis that NMDA receptors (NMDAR) play a role in maintenance of torpor in AGS through inhibition of central NMDAR. After habituation to intraperitoneal (IP) injections of saline, IP administration of MK-801, but not saline, induced arousal (n=3 AGS). To test the hypothesis that arousal is induced via inhibition of central NMDAR, MK-801 was delivered into the lateral ventricle (0.2, 2, 20 or 200 µg/10 µl, delivered over 1 min) of habituated AGS. Cannula placement into lateral ventricle was verified by withdrawing CSF during surgery and by bioassay where ICV injection of the A1 agonist, N 6– cyclohexyladenosine (CHA, 0.5nmol) induced a decrease in Tb and/or VO2 in euthermic AGS. Prior to ICV injection a cannula primed with MK-801 was introduced through the guide cannula. Approximately 12 hours later 10µl MK-801 was injected using a perfusion pump. The cannula was left in place for 24 hours while VO2, Tb, and ECG were monitored. Even the high dose of MK-801 failed to induce arousal (n=5 AGS). Results suggest that ability of MK-801 to induce arousal following IP injection is due to a peripheral and not central effect of the drug.MK-801 is known to inhibit peripheral nicotinic,5HT3,and NMDA receptors. Acknowledgements: Supported by: U.S. Army Research Office W911N F-05-1-0280; Alaska EPSCoR, NSF 0346770
