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

doi:10.1016/j.drugalcdep.2010.12.018

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 journal › Article › peer-review

25 Scopus citations

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 language	English (US)
Pages (from-to)	203-210
Number of pages	8
Journal	Drug and alcohol dependence
Volume	116
Issue number	1-3
DOIs	https://doi.org/10.1016/j.drugalcdep.2010.12.018
State	Published - Jul 1 2011
Externally published	Yes

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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10.1016/j.drugalcdep.2010.12.018

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title = "The sigma receptor agonist SA4503 both attenuates and enhances the effects of methamphetamine",

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.",

keywords = "Dopamine release, Drug discrimination, Locomotor activity, Methamphetamine, Sigma receptors",

author = "Rodvelt, {Kelli R.} and Oelrichs, {Clark E.} and Blount, {Lucas R.} and Fan, {Kuo Hsien} and Lever, {Susan Z.} and Lever, {John R.} and Miller, {Dennis K.}",

note = "Funding Information: This research was partially supported by a grant from the National Institute on Drug Abuse (DA028477) and by the University of Missouri Department of Psychological Sciences. Neither source had further roles in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. ",

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AU - Rodvelt, Kelli R.

AU - Oelrichs, Clark E.

AU - Blount, Lucas R.

AU - Fan, Kuo Hsien

AU - Lever, Susan Z.

AU - Lever, John R.

AU - Miller, Dennis K.

N1 - Funding Information: This research was partially supported by a grant from the National Institute on Drug Abuse (DA028477) and by the University of Missouri Department of Psychological Sciences. Neither source had further roles in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

PY - 2011/7/1

Y1 - 2011/7/1

N2 - 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.

AB - 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.

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KW - Drug discrimination

KW - Locomotor activity

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KW - Sigma receptors

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

Abstract

Keywords

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