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

Melissa A. Tapia, John R. Lever, Susan Z. Lever, Matthew J. Will, Eric S. Park, Dennis K. Miller

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish (US)
JournalPsychopharmacology
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Methamphetamine
Ligands
sigma Receptors
sigma-1 receptor
sigma-2 receptor
1-propyl-5-(3-p-tolylisoxazol-5-yl)-1,2,3,6-tetrahydropyridine
Cocaine
Injections

Keywords

  • Locomotor activity
  • Methamphetamine
  • Sigma receptor

ASJC Scopus subject areas

  • Pharmacology

Cite this

Sigma-1 receptor ligand PD144418 and sigma-2 receptor ligand YUN-252 attenuate the stimulant effects of methamphetamine in mice. / Tapia, Melissa A.; Lever, John R.; Lever, Susan Z.; Will, Matthew J.; Park, Eric S.; Miller, Dennis K.

In: Psychopharmacology, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Rationale: 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. Objectives: The present study examined the effects of PD144418 and YUN-252 pretreatment on methamphetamine-induced hyperactivity after acute treatment. Methods: 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: 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. Conclusions: 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.",
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AU - Tapia, Melissa A.

AU - Lever, John R.

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AU - Will, Matthew J.

AU - Park, Eric S.

AU - Miller, Dennis K.

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AB - Rationale: 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. Objectives: The present study examined the effects of PD144418 and YUN-252 pretreatment on methamphetamine-induced hyperactivity after acute treatment. Methods: 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: 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. Conclusions: 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.

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