Unbound MEDLINE

Delta9-tetrahydrocannabinol (Delta9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia.

Abstract

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.

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  • Publisher Full Text
  • Authors

    Hayakawa K, Mishima K, Nozako M, Hazekawa M, Ogata A, Fujioka M, Harada K, Mishima S, Orito K, Egashira N, Iwasaki K, Fujiwara M

    Source

    Life sciences 80:16 2007 Mar 27 pg 1466-71

    MeSH

    Analysis of Variance
    Animals
    Blotting, Western
    Body Temperature
    Body Temperature Regulation
    Cerebral Cortex
    Cerebral Infarction
    Dronabinol
    Electrophoresis, Polyacrylamide Gel
    Gene Expression Regulation
    Hypothermia, Induced
    Male
    Mice
    Piperidines
    Pyrazoles
    Tetrazolium Salts

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17289082