Role of alpha1-adrenoceptor subtypes in the effects of methylenedioxy methamphetamine (MDMA) on body temperature in the mouse.
OBJECTIVE
We have investigated the ability of alpha(1)-adrenoceptor antagonists to affect the hyperthermia produced by methylenedioxy methamphetamine (MDMA) in conscious mice.


METHODS
Mice were implanted with temperature probes under ether anaesthesia and allowed 2 weeks recovery. MDMA (20 mg kg(-1)) was administered subcutaneously 30 min after vehicle or test antagonist or combination of antagonists and effects on body temperature monitored.


RESULTS
Following vehicle, MDMA produced a hyperthermia, reaching a maximum increase of 1.8 degrees C at 140 min. Prazosin (0.1 mg kg(-1)) revealed an early significant hypothermia to MDMA of -1.94 degrees C. The alpha(1A)-adrenoceptor antagonist RS 100329 (0.1 mg kg(-1)), or the alpha(1D)-adrenoceptor antagonist BMY 7378 (0.5 mg kg(-1)) given alone, did not reveal a hypothermia to MDMA, but the combination of the two antagonists revealed a significant hypothermia to MDMA. The putative alpha(1B)-adrenoceptor antagonist cyclazosin (1 mg kg(-1)) also revealed a significant hypothermia to MDMA, but actions of cyclazosin at the other alpha(1)-adrenoceptor subtypes cannot be excluded.


CONCLUSIONS
More than one subtype of alpha(1)-adrenoceptor is involved in a component of the hyperthermic response to MDMA in mouse, probably both alpha(1A)- and alpha(1D)-adrenoceptors, and removal of this alpha(1)-adrenoceptor-mediated component reveals an initial hypothermia.
Department of Physiology, Royal College of Surgeons in Ireland, Dublin, Ireland.
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Bexis
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Docherty
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D005334:Fever / Q000139:chemically induced; D008297:Male; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects* / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D013941:Thymine / Q000494:pharmacology
C547714:Adra1a protein, mouse; C547720:Adra1d protein, mouse; D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011799:Quinazolines; D011810:Quinoxalines; C120711:RS 100329; D018340:Receptors, Adrenergic, alpha-1; C080462:cyclazosin; C053428:BMY 7378; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D013941:Thymine; D011224:Prazosin