The sigma receptor agonist SA4503 both attenuates and enhances the effects of methamphetamine

Kelli R. Rodvelt, Clark E. Oelrichs, Lucas R. Blount, Kuo Hsien Fan, Susan Z. Lever, John R. Lever, Dennis K. Miller

Research output: Contribution to journalArticle

Abstract

Background: Methamphetamine's behavioral effects have been attributed to its interaction with monoamine transporters; however, methamphetamine also has affinity for sigma receptors. Method: The present study investigated the effect of the sigma receptor agonist SA 4503 and the sigma receptor antagonists BD-1047 and BD-1063 on methamphetamine-evoked [ 3H]dopamine release from preloaded rat striatal slices. The effect of SA 4503 on methamphetamine-induced hyperactivity and on the discriminative stimulus properties of methamphetamine also was determined. Results: SA 4503 attenuated methamphetamine-evoked [ 3H]dopamine release in a concentration-dependent manner. BD-1047 and BD-1063 did not affect release. SA 4503 dose-dependently potentiated and attenuated methamphetamine-induced hyperactivity. SA 4503 pretreatment augmented the stimulus properties of methamphetamine. Conclusions: Our findings indicate that SA 4503 both enhances and inhibits methamphetamine's effects and that sigma receptors are involved in the neurochemical, locomotor stimulatory and discriminative stimulus properties of methamphetamine.

Original languageEnglish (US)
Pages (from-to)203-210
Number of pages8
JournalDrug and alcohol dependence
Volume116
Issue number1-3
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

Keywords

  • Dopamine release
  • Drug discrimination
  • Locomotor activity
  • Methamphetamine
  • Sigma receptors

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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