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Effects of a Beta3‐Adrenergic Antagonist on the Hyperthermic Response to MDMA in mice
Author(s) -
Docherty James R.,
Bexis Sotiria
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.625
Subject(s) - hyperthermia , antagonist , mdma , hypothermia , prazosin , adrenergic antagonist , pharmacology , chemistry , receptor antagonist , adrenergic receptor , blockade , thermoregulation , endocrinology , medicine , receptor
We have previously shown that combined alpha‐1A/1D‐adrenergic blockade alters the temperature response to MDMA from hyperthermia to a biphasic hypothermia followed by hyperthermia in mice. Other authors have shown that, in rats, the hyperthermia to MDMA is reduced by combination of the alpha1‐antagonist prazosin (PR) and the beta3‐antagonist SR59230A (SR). We now investigate the actions of SR at alpha1‐adrenoceptors and on temperature responses to MDMA in mice. Mice were implanted under ether anaesthesia with temperature probes (DSI), and after 14 days temperature was recorded in freely moving mice. PR (0.1mg/kg) or SR (5 mg/kg), but not SR (0.5 mg/kg) (a dose that would be expected to have beta3‐antagonist actions from our functional studies in vitro), altered the response to MDMA from a hyperthermia to biphasic hypothermia followed by hyperthermia. The combination of PR (0.1 mg/kg) and SR (5 mg/kg) had no more effect than PR alone. Although SR was 100 times less potent than PR at alpha1‐adrenoceptor subtypes in functional and ligand binding studies in vitro, it was effective in our telemetry studies at a 50 times higher dose than that of PR, but ineffective at a 5 times higher dose than PR, consistent with alpha1‐actions. In conclusion, the beta3‐adrenergic antagonist SR reduced the hyperthermic response to MDMA in mice, but this action may involve mainly alpha1‐adrenergic antagonism. Supported by HRB (Ireland).