Abstract
Sigma receptor antagonists diminish the effects of cocaine in behavioral assays, including conditioned place preference. Previous locomotor activity experiments in mice determined that the sigma receptor ligand YZ-185 (N-phenylpropyl-N'-(3-methoxyphenethyl)piperazine) enhanced cocaine-induced hyperactivity at a lower (0.1 μ mol/kg) dose and dose-dependently attenuated cocaine-induced hyperactivity at higher (3.16-31.6 μ mol/kg) doses. The present study investigated the effect of YZ-185 on cocaine's conditioned-rewarding properties in mice. YZ-185 (0.1, 0.316, 3.16, and 31.6 μ mol/kg) did not have intrinsic activity to produce conditioned place preference or aversion. A higher (31.6 μ mol/kg) YZ-185 dose, but not lower (0.1-3.16 μ mol/kg) YZ-185 doses, prevented the development of place preference to cocaine (66 μ mol/kg). YZ-185 did not alter the expression of cocaine place preference. To further characterize YZ-185's behavioral profile, its effects in the elevated zero maze and rotarod procedures were also determined; YZ-185 produced no significant change from baseline in either assay, indicating that the sigma receptors probed by YZ-185 do not regulate anxiety-like or coordinated motor skill behaviors. Overall, these results suggest that YZ-185 is a sigma receptor antagonist at the 31.6 μ mol/kg dose and demonstrate that sigma receptors can mediate the development of the conditioned-rewarding properties of cocaine.