Effects of NRA0045, NRA0160, and NRA0215 on regional Fos-like immunoreactivity in the rat brain

Abstract

Pharmacological characteristics of NRA compounds, novel atypical antipsychotics, were compared with those of clozapine and haloperidol, in regard to modification of Fos-like immunoreactivity (FLI) in rats. ( R)-(+)-2-Amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl] thiazole (NRA0045) and 2-carbamoyl-4-phenyl-5-[2-[4-(4-fluorobenzylidene) piperidin-1-yl] ethyl] thiazole (NRA0215) have a high affinity for dopamine D 4 receptors, serotonin 2A receptors, and the α1 adrenoceptor. 2-Carbamoyl-4-(4-fluorophenyl)-5-[2-[4-(3-fluorobenzylidene) piperidin-1-yl] ethyl] thiazole (NRA0160) has a selective and high affinity for dopamine D 4 receptors. NRA0045 and clozapine (10 and 30 mg/kg, IP) produced significant increases in FLI in both the nucleus accumbens (N. Acc.) and the medial prefrontal cortex (mPFC) but not in the dorsolateral striatum (DLS). In contrast, NRA0160 and NRA0215 (10 and 30 mg/kg, IP) significantly increased FLI in the mPFC but not in the N. Acc. and the DLS. Haloperidol (0.1 and 1 mg/kg, IP) significantly produced FLI in the N. Acc., the DLS, and the mPFC. These data indicate that the antagonistic effects of dopamine D 4 receptors may contribute, at least in part, to the actions of NRA0045, NRA0160, and NRA0215 in the mPFC.