Effects of N-phenylpropyl-N'-substituted piperazine sigma receptor ligands on cocaine-induced hyperactivity in mice

Andrew S. Sage, Clark E. Oelrichs, Derick C. Davis, Kuo Hsien Fan, Roger I. Nahas, Susan Z. Lever, John R. Lever, Dennis K. Miller

Research output: Contribution to journalArticlepeer-review

Abstract

The present study examined N-phenylpropyl-N'-substituted piperazine sigma receptor ligands on cocaineinduced changes in locomotor activity in mice. Previous reports indicate that N-phenylpropyl-N'-(4- methoxybenzyl)piperazine (Nahas-3h), N-phenylpropyl-N'-(4-methoxyphenethyl)piperazine (YZ-067), and N-phenylpropyl-N'-(3-methoxyphenethyl)piperazine (YZ-185) bind with high affinity (Ki values ≈ 1 nM) to σ1 sigma receptors. YZ-067 and YZ-185 are known to attenuate cocaine-induced convulsions, while Nahas-3h has not been tested in behavioral studies. Nahas-3h significantly attenuated cocaine-induced hyperactivity. YZ- 067 decreased the effect of cocaine in a dose-dependentmanner. Interestingly, YZ-185 inhibited cocaine's effect at higher doses, but enhanced cocaine's effect at a low dose. The YZ-185 inhibition of cocaine-induced hyperactivity was not surmounted by increasing the cocaine dose. Overall, this study is consistent with previous work showing the ability of certain sigma receptor ligands to affect cocaine-induced hyperactivity. Further, subtle alterations of ligand structure and the specific dosage levels employed influence the behavioral effects observed, with a 3-methoxy substituent apparently conferring the ability of a ligand to enhance cocaine's locomotor stimulatory effects.

Original languageEnglish (US)
Pages (from-to)201-207
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume110
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Keywords

  • Behavior
  • Cocaine
  • Locomotor activity
  • Mouse
  • Sigma receptor

ASJC Scopus subject areas

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

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