MS-377, a novel selective sigma(1) receptor ligand, reverses phencyclidine-induced release of dopamine and serotonin in rat brain

A novel selective g, receptor ligand, (R)-(+)-1-(4-chlorophenyl)-3-[4-(2-me thoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate (MS-377), inhib its phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP)-induced behaviors in animal models. In this study, we measured extracellular dopamine and se rotonin levels in the rat brain after treatment with MS-377 alone, using in vivo microdialysis. We also examined the effects of MS-377 on extracellula r dopamine and serotonin levels in the rat medial prefrontal cortex after t reatment with PCP. MS-377 itself had no significant effects on dopamine rel ease in the striatum (10 mg/kg, p.o.) not on dopamine or serotonin release in the medial prefrontal cortex (1 and 10 mg/kg, p.o.). PCP (3 mg/kg, i.p.) markedly increased dopamine and serotonin release in the medial prefrontal cortex. MS-377 (I mg/kg,, p.o.), when administered 60 min prior to PCP, si gnificantly attenuated this effect of PCP. These results suggest that the i nhibitory effects of MS-377 on PCP-induced behaviors are partly mediated by inhibition of the increase in dopamine and serotonin release in the rat me dial prefrontal cortex caused by PCP. (C) 2001 Elsevier Science B.V. All ri ghts reserved.