title: Serotonin is involved in the psychostimulant and hypothermic effect of 4-methylamphetamine in rats.
abstract: 4-Methylamphetamine (4-MA) has recently emerged as a designer drug of abuse in Europe and it is consumed always with amphetamine. There have been reported some deaths and non-fatal intoxications related to 4-MA. We investigated the changes in locomotor activity and body temperature after 4-MA administration to male Sprague-Dawley rats. Our experiments were carried out at a normal or high ambient temperature. 4-MA (2.5-10mg/Kg, given subcutaneously) increased, in a dose-dependent manner, the horizontal locomotor activity that was significantly reduced by ketanserin, p-cholorophenylalanine (pCPA) or haloperidol, but not by pindolol. In addition, we have studied the effect of 4-MA on core body temperature by means of an implanted electronic thermograph, enabling continuous measurement of body temperature. We observed a dose-dependent hypothermic response to 4-MA that reached a maximum 45 min after a single injection. We also evidenced slight tachyphylaxis to the hypothermic effect when 4-MA was administered four times in a 2h interval. The pre-treatment of animals with pCPA or pindolol, but not with ketanserin, fully abolished the hypothermic effect of 4-MA. With all that, we conclude that hypothermia induced by 4-MA is due to the release of 5-HT which activates postsynaptic 5-HT1A receptors.
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section) and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Spain.
authors: Mar
authors: M
authors: Rubio
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section) and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Spain.
authors: Raúl
authors: R
authors: López-Arnau
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section) and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Spain.
authors: David
authors: D
authors: Pubill
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section) and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Spain. Electronic address: eescubedo@ub.edu.
authors: Elena
authors: E
authors: Escubedo
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section) and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Spain.
authors: Jorge
authors: J
authors: Camarasa
mesh_terms: D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D044348:Receptors, Serotonin, 5-HT2; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C000592889:1-(4-methylphenyl)propane-2-amine; D004298:Dopamine
keywords: 4-Methylamphetamine; Hypothermia; Locomotor activity; Rat; Serotonin