Delta9-tetrahydrocannabinol (Delta9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia.
Delta(9)-tetrahydrocannabinol (Delta(9)-THC), a primary psychoactive constituent of cannabis, has been reported to act as a neuroprotectant via the cannabinoid CB(1) receptor. In this study, Delta(9)-THC significantly decreased the infarct volume in a 4 h mouse middle cerebral artery occlusion mouse model. The neuroprotective effect of Delta(9)-THC was completely abolished by SR141716, cannabinoid CB(1) receptor antagonist, and by warming the animals to 31 degrees C. Delta(9)-THC significantly decreased the rectal temperature, and the hypothermic effect was also inhibited by SR141716 and by warming to 31 degrees C. At 24 h after cerebral ischemia, Delta(9)-THC significantly increased the expression level of CB(1) receptor in both the striatum and cortex, but not in the hypothalamus. Warming to 31 degrees C during 4 h cerebral ischemia did not increase the expression of CB(1) receptor at the striatum and cortex in MCA-occluded mice. These results show that the neuroprotective effect of Delta(9)-THC is mediated by a temperature-dependent mechanism via the CB(1) receptor. In addition, warming to 31 degrees C might attenuate both the neuroprotective and hypothermic effects of Delta(9)-THC through inhibiting the increase in CB(1) receptor in both the striatum and cortex but not in the hypothalamus, which may suggest a new thermoregulation mechanism of Delta(9)-THC.
Hayakawa
Kazuhide
K
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma 8-19-1, Fukuoka City, Fukuoka, Japan.
Mishima
Kenichi
K
Nozako
Masanori
M
Hazekawa
Mai
M
Ogata
Ayumi
A
Fujioka
Masayuki
M
Harada
Kazuhiko
K
Mishima
Shohei
S
Orito
Kensuke
K
Egashira
Nobuaki
N
Iwasaki
Katunori
K
Fujiwara
Michihiro
M
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D002544:Cerebral Infarction / Q000517:prevention & control*; D013759:Dronabinol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000187:drug effects*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D000077285:Rimonabant; D013778:Tetrazolium Salts
D010880:Piperidines; D011720:Pyrazoles; D013778:Tetrazolium Salts; D013759:Dronabinol; C009591:triphenyltetrazolium; D000077285:Rimonabant