The sigma receptor ligand N-phenylpropyl-N′-(4-methoxyphenethyl)3piperazine (YZ-067) enhances the cocaine conditioned-rewarding properties while inhibiting the development of sensitization of cocaine in mice

Melissa A. Tapia, Andrew S. Sage, Emma I. Fullerton, Jessica M. Judd, Paige C. Hildebrant, Matthew J. Will, Susan Z. Lever, John R. Lever, Dennis K. Miller

Research output: Contribution to journalArticle

Abstract

Rationale: The N-phenylpropyl-N′-substituted piperazines SA-4503 (N-phenylpropyl-N′-(3,4-dimethoxyphenethyl)piperazine) and YZ-185 (N-phenylpropyl-N′-(3-methoxyphenethyl)piperazine) bind to sigma (σ) receptors and block the development of cocaine-induced conditioned place preference at concentrations that inhibit cocaine-induced hyperactivity. YZ-067 (N-phenylpropyl-N′-(4-methoxyphenethyl)piperazine) also binds to sigma receptors and attenuates cocaine-induced hyperactivity in mice. Objectives: The present study determined the effect of YZ-067 on the development and expression of cocaine (66 μmol/kg or 33 μmol/kg) conditioned place preference (CPP) and locomotor sensitization in mice. Results: YZ-067 (10 or 31.6 μmol/kg) did not have intrinsic effects on place preference or place aversion. Interestingly, the 31.6 μmol/kg YZ-067 dose enhanced the development of cocaine place preference, while 10 μmol/kg YZ-067 attenuated the development of cocaine-induced locomotor sensitization. However, YZ-067 did not alter the expression of cocaine place preference nor cocaine-induced locomotor sensitization. In follow-up studies, YZ-067 did not affect performance in the zero maze or rotarod, indicating that sigma receptors probed by this ligand do not regulate anxiety-like or coordinated motor skill behaviors, respectively. Conclusion: Overall, these results are consistent with previous studies demonstrating a role for sigma receptors in the behavioral effects of cocaine. However, the present findings also indicate that N-phenylpropyl-N′-substituted piperazines do not strictly block cocaine’s behavioral effects and that sigma receptor may differentially mediate cocaine-induced hyperactivity and place conditioning.

Original languageEnglish (US)
JournalPsychopharmacology
DOIs
StateAccepted/In press - Jan 1 2019
Externally publishedYes

Keywords

  • Behavior
  • Cocaine
  • Locomotor
  • Preference
  • Sigma Receptor

ASJC Scopus subject areas

  • Pharmacology

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