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

Neurosci Lett. 2015 Mar 17:590:68-73. doi: 10.1016/j.neulet.2015.01.075. Epub 2015 Jan 29.

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.

Keywords: 4-Methylamphetamine; Hypothermia; Locomotor activity; Rat; Serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamines / pharmacology*
  • Animals
  • Body Temperature / drug effects*
  • Central Nervous System Stimulants / pharmacology*
  • Dopamine / metabolism
  • Dose-Response Relationship, Drug
  • Male
  • Motor Activity / drug effects
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptors, Serotonin, 5-HT2 / metabolism
  • Serotonin / metabolism*
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology

Substances

  • Amphetamines
  • Central Nervous System Stimulants
  • Receptors, Serotonin, 5-HT2
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin 5-HT2 Receptor Antagonists
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • 1-(4-methylphenyl)propane-2-amine
  • Dopamine