The expression of methiopropamine-induced locomotor sensitization requires dopamine D2, but not D1, receptor activation in the rat

Behav Brain Res. 2016 Sep 15:311:403-407. doi: 10.1016/j.bbr.2016.05.060. Epub 2016 Jun 3.

Abstract

Methiopropamine (MPA) is a structural analog to methamphetamine and is categorized as a novel psychoactive substance that needs to be controlled. However, no study has been performed to determine whether MPA actually develops an addiction-like behavior similar to those arising from other psychomotor stimulants. Thus, we attempted to determine whether MPA produces locomotor sensitization in a manner similar to amphetamine. In the first experiment, rats were pre-exposed to either saline or one of three different doses of MPA (0.2, 1.0, or 5.0mg/kg, IP) with a total of four injections, respectively. After a 2-week withdrawal period, when they were challenged with the same dose of MPA, only the group that was pre-exposed to high dose of MPA (5.0mg/kg) showed sensitized locomotor activity. In the second experiment, all rats were pre-exposed to MPA (5.0mg/kg) only. Interestingly, the expression of MPA-induced locomotor sensitization was inhibited by a pre-injection of a dopamine D2 receptor antagonist, eticlopride (0.05mg/kg, IP), though not by a dopamine D1 receptor antagonist, SCH23390 (0.01mg/kg, IP). These results suggest that repeated injection of MPA in the rat provokes certain neuronal changes involving specific, likely D2, dopamine receptor-mediated pathways that contribute to the expression of MPA-induced locomotor sensitization.

Keywords: Eticlopride; Locomotor sensitization; Methiopropamine; SCH23390.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Central Nervous System Stimulants / pharmacology*
  • Dopamine Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Male
  • Methamphetamine / analogs & derivatives*
  • Methamphetamine / pharmacology
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D2 / metabolism*
  • Salicylamides / pharmacology
  • Thiophenes / pharmacology*

Substances

  • 1-(2-thienyl)-2-(methylamino)propane
  • Benzazepines
  • Central Nervous System Stimulants
  • DRD2 protein, rat
  • Dopamine Agents
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • SCH 23390
  • Salicylamides
  • Thiophenes
  • Methamphetamine
  • eticlopride