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

Abstract

Abstract4-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 SpragueDawley rats. Our experiments were carried out at a normal or high ambient temperature. 4-MA (2.5 -10 mg/Kg, given subcutaneously) increased, in a dosedependent manner, the horizontal locomotor activity that was significantly reduced by ketanserin, p-cholorophenylalanine (pCPA) or haloperidol. 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 2 h 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-HT 1A receptors.

N-Alkylated Analogs of 4-Methylamphetamine (4-MA) Differentially Affect Monoamine Transporters and Abuse Liability

“…Preclinical studies from our laboratory and others show that 4-MA is a nonselective transporter substrate capable of releasing dopamine and serotonin from neurons in vitro and in vivo (Baumann et al, 2011;Wee et al, 2005). When compared with the parent drug amphetamine, 4-MA has much greater potency as a substrate at SERT, and a recent study confirms that locomotor and hypothermic effects produced by 4-MA in rats depend upon serotonergic systems (Rubio et al, 2015). Older literature indicates that 4-MA is also a potent inhibitor of monoamine oxidase (MAO) A, the principal enzyme responsible for the breakdown of monoamine neurotransmitters (Ross et al, 1977).…”