4-Methylthioamphetamine-induced hyperthermia in mice: influence of serotonergic and catecholaminergic pathways.
4-Methylthioamphetamine (4-MTA), also known as p-methylthioamphetamine, is a new amphetamine derivative which in humans has been increasingly associated with severe intoxications and several deaths. As hyperthermia is considered to be one of the most life-threatening acute physiological consequences of amphetamine-related intoxications, it was our aim to determine whether 4-MTA induces changes in body temperature in a mouse model. Accordingly, we measured the subcutaneous temperature after acute administration of 4-MTA in CD1 mice. Because hyperthermia seems to result from the central and peripheral actions of catecholamines and serotonin (5-hydroxytriptamine or 5-HT), we also investigated the possible interactions of some catecholaminergic and serotonergic receptor blockers and the inhibition of monoamine oxidase (MAO) with this effect. 4-MTA induced hyperthermia in CD1 mice. Blockade of the 5-HT receptors with methysergide and MAO inhibition with pargyline resulted in the potentiation of the 4-MTA-induced hyperthermic effect. Blockade of the alpha(1)-adrenergic receptors with prazosin completely reverted the 4-MTA-induced hyperthermia while with the beta-adrenergic receptor blocker dl-propranolol this reversal was not complete. Blockade of the alpha(2)-adrenergic receptors with yohimbine had no effect on the hyperthermia induced by 4-MTA. These results suggest that 4-MTA-induced hyperthermia is highly influenced by the catecholaminergic and serotonergic receptor activation and the MAO activity.
Carmo
Helena
H
ICETA/CEQUP, Toxicology Department, Faculty of Pharmacy, University of Porto, Porto, Portugal. helenacarmo@mail.ff.up.pt
Remião
Fernando
F
Carvalho
Félix
F
Fernandes
Eduarda
E
de Boer
Douwe
D
dos Reys
Lesseps A
LA
de Lourdes Bastos
Maria
M
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000662:Amphetamines / Q000633:toxicity*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D002395:Catecholamines / Q000502:physiology*; D006979:Hyperthermia, Induced; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000662:Amphetamines; D002395:Catecholamines; D008996:Monoamine Oxidase Inhibitors; D011941:Receptors, Adrenergic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; C078956:4-methylthioamphetamine; D010293:Pargyline; D008995:Monoamine Oxidase; D011224:Prazosin; D008784:Methysergide