S. Takahashi et al., MS-377, a novel selective sigma(1) receptor ligand, reverses phencyclidine-induced release of dopamine and serotonin in rat brain, EUR J PHARM, 427(3), 2001, pp. 211-219
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.