title: Effects of N-phenylpropyl-N'-substituted piperazine sigma receptor ligands on cocaine-induced hyperactivity in mice.
abstract: The present study examined N-phenylpropyl-N'-substituted piperazine sigma receptor ligands on cocaine-induced 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-dependent manner. 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.
authors.affiliation: Department of Psychological Sciences, University of Missouri, Columbia, MO 65211 USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Sage
authors.forename: Clark E
authors.initials: CE
authors.lastname: Oelrichs
authors.forename: Derick C
authors.initials: DC
authors.lastname: Davis
authors.forename: Kuo-Hsien
authors.initials: KH
authors.lastname: Fan
authors.forename: Roger I
authors.initials: RI
authors.lastname: Nahas
authors.forename: Susan Z
authors.initials: SZ
authors.lastname: Lever
authors.forename: John R
authors.initials: JR
authors.lastname: Lever
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Miller
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000139:chemically induced*; D008024:Ligands; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D017480:Receptors, sigma / Q000378:metabolism*
chemical_list: D008024:Ligands; D010879:Piperazines; D017480:Receptors, sigma; D003042:Cocaine
keywords: Behavior; Cocaine; Locomotor activity; Mouse; Sigma receptor