, Volume 236, Issue 11, pp 3147–3158 | Cite as

Sigma-1 receptor ligand PD144418 and sigma-2 receptor ligand YUN-252 attenuate the stimulant effects of methamphetamine in mice

  • Melissa A. TapiaEmail author
  • John R. Lever
  • Susan Z. Lever
  • Matthew J. Will
  • Eric S. Park
  • Dennis K. Miller
Original Investigation



Previous research indicates that the selective sigma-1 receptor ligand PD144418 and the selective sigma-2 ligands YUN-252 can inhibit cocaine-induced hyperactivity. The effects of these ligands on other stimulants, such as methamphetamine, have not been reported.


The present study examined the effects of PD144418 and YUN-252 pretreatment on methamphetamine-induced hyperactivity after acute treatment.


Mice (n = 8–14/group) were injected with PD144418 (3.16, 10, or 31.6 μmol/kg), YUN-252 (0.316, 3.16, 31.6 μmol/kg), or saline. After 15 min, mice injected with 2.69 μmol/kg methamphetamine or saline vehicle, where distance traveled during a 60-min period was recorded. Additionally, the effect of PD144418 on the initiation and expression of methamphetamine sensitization was determined by treating mice (n = 8–14/group) with PD144418, methamphetamine or saline repeatedly over a 5-day period, and testing said mice with a challenge dose after a 7-day withdrawal period.


Results indicate that both PD144418 and YUN-252, in a dose-dependent manner, attenuated hyperactivity induced by an acute methamphetamine injection. Specifically, 10 μmol/kg or 31.6 μmol/kg of PD144418 and 31 μmol/kg of YUN-252 suppressed methamphetamine-induced hyperactivity. In regard to methamphetamine sensitization, while 10 μmol/kg PD144418 prevented the initiation of methamphetamine sensitization, it did not have an effect on the expression.


Overall, the current results suggest an intriguing potential for this novel sigma receptor ligand as a treatment for the addictive properties of methamphetamine. Future analysis of this novel sigma receptor ligand in assays directly measuring reinforcement properties will be critical.


Sigma receptor Methamphetamine Locomotor activity 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Psychological SciencesUniversity of MissouriColumbiaUSA
  2. 2.Research Service, Harry S. Truman Memorial Veterans’ Hospital, Columbia, and Department of Radiology and Radiopharmaceutical Sciences InstituteUniversity of MissouriColumbiaUSA
  3. 3.Department of Chemistry and MU Research Reactor CenterUniversity of MissouriColumbiaUSA

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