Serotonin is involved in the psychostimulant and hypothermic effect of 4-methylamphetamine in rats

• Published in: Neuroscience letters Vol. 590; pp. 68 - 73
• Main Authors: Rubio, Mar, López-Arnau, Raúl, Pubill, David, Escubedo, Elena, Camarasa, Jorge
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 17.03.2015; Elsevier B.V
• Subjects: 4-Methylamphetamine; Amfetamines; Amphetamines; Amphetamines - pharmacology; Animals; Body Temperature - drug effects; Central nervous system; Central Nervous System Stimulants - pharmacology; Dopamine - metabolism; Dose-Response Relationship, Drug; Farmacologia; Hipotèrmia; Hypothermia; Locomotor activity; Male; Motor Activity - drug effects; Pharmacology; Rat; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A - metabolism; Receptors, Serotonin, 5-HT2 - metabolism; Serotonin; Serotonin - metabolism; Serotonin 5-HT1 Receptor Antagonists - pharmacology; Serotonin 5-HT2 Receptor Antagonists - pharmacology; Serotonina; Sistema nerviós central; Serotonin; Rat; 4-Methylamphetamine; Locomotor activity; Hypothermia
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2015.01.075

•4-methylamphetamine increased locomotor activity and induced hypothermia in rats.•The increase in the locomotor activity involves both dopamine and serotonin.•The hypothermic response reached a maximum 45min after injection.•The hypothermia is due to an activation of postsynaptic 5-HT1A receptors. 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 45min 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.