TY - JOUR
T1 - Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice
AU - Avraham, Yosefa
AU - Israeli, Eran
AU - Gabbay, Ezra
AU - Okun, Avital
AU - Zolotarev, Olga
AU - Silberman, Isable
AU - Ganzburg, Vera
AU - Dagon, Yossi
AU - Magen, Iddo
AU - Vorobia, Lia
AU - Pappo, Orit
AU - Mechoulam, Raphael
AU - Ilan, Yaron
AU - Berry, Elliot M.
N1 - Funding Information:
The research was supported by the USA–Israel Binational Science Foundation (to E.B. and R.M.) and the US National Institute on Drug Abuse (to R.M.).
Funding Information:
We would like to thank Prof. Norman Grover for his help in the statistical analysis. The research was supported by the Israel Science Foundation (to E.B.).
PY - 2006/1
Y1 - 2006/1
N2 - Endocannabinoids function as neurotransmitters and neuromodulators in the central nervous system via specific receptors and apparently have a neuroprotective role. We assumed that the endocannabinoid system could be involved in the pathogenesis of hepatic encephalopathy (HE), a neuropsychiatric syndrome due to liver disease. We used a mouse model of a thioacetamide induced fulminant hepatic failure. We found that the levels of the endocannabinoid 2-arachidonoyl-glycerol (2-AG) were elevated in the brain. Treatment with either 2-AG or with the CB1 receptor antagonist, SR141716A, improved a neurological score, activity and cognitive function. Activation of the CB 2 receptor by a selective agonist, HU308, also improved the neurological score. 2-AG activity could be blocked with the specific CB 2 receptor antagonist SR144528A. The CB1 receptor agonist noladin ether was inactive. We conclude that the endocannabinoid system may play an important role in the pathogenesis of HE. Modulation of this system either by exogenous agonists specific for the CB2 receptors or possibly also by antagonists to the CB1 receptors may have therapeutic potential.
AB - Endocannabinoids function as neurotransmitters and neuromodulators in the central nervous system via specific receptors and apparently have a neuroprotective role. We assumed that the endocannabinoid system could be involved in the pathogenesis of hepatic encephalopathy (HE), a neuropsychiatric syndrome due to liver disease. We used a mouse model of a thioacetamide induced fulminant hepatic failure. We found that the levels of the endocannabinoid 2-arachidonoyl-glycerol (2-AG) were elevated in the brain. Treatment with either 2-AG or with the CB1 receptor antagonist, SR141716A, improved a neurological score, activity and cognitive function. Activation of the CB 2 receptor by a selective agonist, HU308, also improved the neurological score. 2-AG activity could be blocked with the specific CB 2 receptor antagonist SR144528A. The CB1 receptor agonist noladin ether was inactive. We conclude that the endocannabinoid system may play an important role in the pathogenesis of HE. Modulation of this system either by exogenous agonists specific for the CB2 receptors or possibly also by antagonists to the CB1 receptors may have therapeutic potential.
KW - Activity score
KW - Cannabinoid receptors
KW - Endocannabinoids
KW - Hepatic encephalopathy
KW - Neurological and cognitive functions
KW - Thioacetamide
UR - http://www.scopus.com/inward/record.url?scp=29144480571&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2005.07.008
DO - 10.1016/j.nbd.2005.07.008
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C2 - 16102970
AN - SCOPUS:29144480571
SN - 0969-9961
VL - 21
SP - 237
EP - 245
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -