Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2536768 | European Journal of Pharmacology | 2006 | 6 Pages |
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 (CB1) receptor in this effect has not been fully elucidated. Consequently, we investigated the role of CB1 receptor in modulating plasma corticosterone concentrations through use of the potent and selective CB1 receptor antagonist SR141716A and CB1 receptor knockout mice. Rats were administered SR141716A (0.1, 0.3, and 1Â mg/kg, i.v.) and blood was sampled at 0, 15, 60, 90 and 120Â min postinjection. SR141716A dose- and time-dependently increased plasma corticosterone levels and maximum effects were obtained with the 1Â mg/kg dose 60Â min postinjection. In mice, SR141716A (0.1, 0.3, 1, 3, and 10Â mg/kg, i.p.) also induced a dose-dependent rise in corticosterone levels 60Â min postinjection; this rise reached plateau levels with the 0.3-1Â mg/kg doses. The stimulatory effect of SR141716A (1Â mg/kg, i.p.) on plasma corticosterone 60Â min postinjection was abolished in the CB1 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 (10Â mg/kg, i.p.) on plasma corticosterone 60Â min postinjection were retained after subchronic dosing (5Â days, once daily) in mice. The present results indicate that SR141716A increases plasma corticosterone in rats and mice possibly through blockade of CB1 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 CB1 receptor antagonism.
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Authors
Mark R. Wade, Aldemar Degroot, George G. Nomikos,