Phencyclidine (PCP)-induced head-weaving is inhibited by a novel selective sigma1-ligand, (
R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate (MS-377), but not by
dopamine D2 antagonists. In the present study, we examined the effects of two potent and selective sigma1-ligands,
MS-377 and N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)
ethylamine (NE-100), on PCP-induced rearing behaviour, hyperlocomotion and
ataxia in comparison with the currently available
antipsychotic agents with affinity for D2 receptors,
haloperidol,
sultopride and
risperidone. Male Wistar rats or ddY mice were administered
MS-377,
NE-100,
haloperidol,
sultopride or
risperidone, and PCP was administered 60 min later (in the case of
NE-100 10 min later). Rearing behaviour, hyperlocomotion and
ataxia were examined 10 min after PCP administration.
MS-377,
haloperidol,
sultopride and
risperidone dose-dependently inhibited PCP-induced rearing and hyperlocomotion, but did not antagonize PCP-induced
ataxia. In contrast, the other selective sigma1-ligand,
NE-100, did not affect any of the PCP-induced behaviour patterns in this study. These results suggest that there are at least two types of
ligands for sigma1-receptors and that some sigma1-ligands, including
MS-377, have more comprehensive effects against PCP-induced abnormal behaviour than other sigma1-ligands or D2 antagonists.