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 language | English (US) |
---|---|
Pages (from-to) | 201-207 |
Number of pages | 7 |
Journal | Pharmacology Biochemistry and Behavior |
Volume | 110 |
DOIs | |
State | Published - 2013 |
Externally published | Yes |
Keywords
- Behavior
- Cocaine
- Locomotor activity
- Mouse
- Sigma receptor
ASJC Scopus subject areas
- Biochemistry
- Toxicology
- Pharmacology
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience