Attenuation of Cocaine‐Induced Behaviors by the Sigma Receptor Ligand YZ‐185

YZ‐185 ( N ‐phenylpropyl‐ N ′‐(3‐methoxyphenethyl)piperazine) is a sigma receptor ligand that binds with greater affinity to the σ1 than to the σ2 sigma receptor subtype (Ki values ≈ 1.4 and 10.2 nM, respectively) in brain. In a dose‐dependent manner and at doses that did not alter basal locomotor activity, YZ‐185 pretreatment attenuated cocaine‐induced hyperactivity in mice. YZ‐185 did not produce conditioned place preference or aversion in mice; however, it attenuated both the induction and expression of conditioned place preference to cocaine. These results indicate a role for sigma receptors in cocaine's locomotor‐activating and conditioned‐rewarding properties and support the use of N ‐phenylpropyl‐ N ′‐substituted piperazine ligands to investigate cocaine's effects.