SA 4503 attenuates cocaine-induced hyperactivity and enhances methamphetamine substitution for a cocaine discriminative stimulus

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

Research output: Contribution to journalArticlepeer-review

Abstract

Cocaine exhibits preferential (~ 15-fold) affinity for σ 1 over σ 2 sigma receptors, and previous research has shown an interaction of σ 1 receptor-selective ligands and cocaine's behavioral effects. The present study investigated the effect of the putative sigma receptor agonist SA 4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride) on cocaine's locomotor stimulatory and discriminative stimulus properties. At doses without intrinsic activity, SA 4503 dose-dependently attenuated cocaine-induced hyperactivity in mice. This inhibition was overcome by increasing the cocaine dose. In rats trained to use cocaine as a discriminative stimulus in a drug discrimination task, doses of SA 4503 that did not substitute for the cocaine stimulus did not alter the cocaine substitution curve. However, SA 4503 potentiated the effect of methamphetamine to substitute for the cocaine stimulus. These data support a role for sigma receptors in the locomotor-activating properties of cocaine and, importantly, indicate a role for these receptors in the discriminative stimulus effects of methamphetamine. The data also suggest sigma receptors mediate the activity of different dopamine pathways responsible for the behavioral effects of psychostimulants.

Original languageEnglish (US)
Pages (from-to)676-682
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume97
Issue number4
DOIs
StatePublished - Feb 2011
Externally publishedYes

Keywords

  • Cocaine
  • Drug discrimination
  • Locomotor activity
  • Sigma receptors

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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