Abstract：
:Although the involvement of cannabinoids and the endogenous cannabinoid system in the regulation of the hypothalamo-pituitary-adrenal axis in rodents is well documented, the precise role played by the cannabinoid type one (CB(1)) receptor in this effect has not been fully elucidated. Consequently, we investigated the role of CB(1) receptor in modulating plasma corticosterone concentrations through use of the potent and selective CB(1) receptor antagonist SR141716A and CB(1) receptor knockout mice. Rats were administered SR141716A (0.1, 0.3, and 1 mg/kg, i.v.) and blood was sampled at 0, 15, 60, 90 and 120 min postinjection. SR141716A dose- and time-dependently increased plasma corticosterone levels and maximum effects were obtained with the 1 mg/kg dose 60 min postinjection. In mice, SR141716A (0.1, 0.3, 1, 3, and 10 mg/kg, i.p.) also induced a dose-dependent rise in corticosterone levels 60 min postinjection; this rise reached plateau levels with the 0.3-1 mg/kg doses. The stimulatory effect of SR141716A (1 mg/kg, i.p.) on plasma corticosterone 60 min postinjection was abolished in the CB(1) receptor knockout mice, which did not show any difference in basal corticosterone levels as compared to their wild-type controls. Finally, the stimulatory effects of SR141716A (10 mg/kg, i.p.) on plasma corticosterone 60 min postinjection were retained after subchronic dosing (5 days, once daily) in mice. The present results indicate that SR141716A increases plasma corticosterone in rats and mice possibly through blockade of CB(1) receptors, an effect that is retained after subchronic dosing in mice. These data provide support for the notion that changes in plasma corticosterone concentrations may be used in the laboratory and the clinic to assess the effects of CB(1) receptor antagonism.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Wade MR,Degroot A,Nomikos GGdoi
10.1016/j.ejphar.2006.08.083subject
Has Abstractpub_date
2006-12-03 00:00:00pages
162-7issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(06)00992-7journal_volume
551pub_type
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