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

被引:9
作者
Sage, Andrew S. [1 ]
Oelrichs, Clark E. [1 ]
Davis, Derick C. [1 ]
Fan, Kuo-Hsien [2 ]
Nahas, Roger I. [2 ]
Lever, Susan Z. [2 ,3 ]
Lever, John R. [4 ,5 ,6 ]
Miller, Dennis K. [1 ,7 ]
机构
[1] Univ Missouri, Dept Psychol Sci, Columbia, MO 65211 USA
[2] Univ Missouri, Dept Chem, Columbia, MO 65211 USA
[3] Univ Missouri, MU Res Reactor Ctr, Columbia, MO 65212 USA
[4] Univ Missouri, Dept Radiol, Columbia, MO 65211 USA
[5] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65211 USA
[6] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA
[7] Univ Missouri, Coll Med, Ctr Translat Neurosci, Columbia, MO 65211 USA
关键词
Behavior; Cocaine; Locomotor activity; Mouse; Sigma receptor; DOPAMINE TRANSPORTER; METHAMPHETAMINE; CHAPERONES; BINDING; KNOCKOUT; SA4503; BRAIN;
D O I
10.1016/j.pbb.2013.07.006
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
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 approximate to 1 nM) to sigma(1) 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. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:201 / 207
页数:7
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