PM431. Effects of iloperidon and nemonaprid on depression, anxiety-like behaviour and locomotion: Altered gen expression levels of FGF2, synapsin and NGF in the hippocampus of mice

Abstract

Abstract Atypical antipsychotics are known to possess more beneficial effects on emotional dysfunction in schizophrenia compared to classical antipsychotics. Iloperidon and nemonaprid are new atypical antipsychotic drugs used in clinics. This study aimed to investigate the effects of these drugs on depression-, anxiety-like behaviors and locomotion in naive mice, using forced swiming test (FST), elevated plus maze (EPM) and open field tests. Moreover the effects of drugs on expression levels of FGF2, synapsin and NGF in the hippocampus of mice were determined using quantitative real-time polymerase chain reaction. Mice were treated chronically with iloperidon (0.5 and 1 mg/kg) and nemonaprid (0.5 and 1 mg/kg) for 15 days and drugs were also administered intraperitoneally 60 min before the tests. Our study revealed that: (1) In FST test, iloperidon (0.5 and 1 mg/kg, p<0.01, p<0.001; respectively) significantly decreased immobility time while nemonaprid had no significant effect.(2) In EPM test, iloperidon (0.5 mg/kg; p<0.05) significantly increased % time spent in open arm’s while nemonaprid insignificantly increased this parameter. Nemonaprid (1 mg/kg; p<0.05) significantly increased % open arm entries while iloperidon (0.5 mg/kg) also insignificantly increased this parameter. (3) In open field test, iloperidon (1 mg/kg; p<0.05) significantly increased the total distance moved while nemonaprid (0.5 and 1 mg/kg; p<0.05, p<0.01; respectively) significantly decreased this parameter. Nemonaprid (0.5 and 1 mg/kg; p<0.05, p<0.001; respectively) significantly decreased the speed of the animals. (4) Chronic administration of iloperidon and nemonaprid significantly increased the expression of FGF2, synapsin and NGF and thus may promote neuroplasticity via the up-regulation of neutropic factors. So both iloperidon and nemonaprid exerted anxiolytic effects while only iloperidon had antidepressant effects; and these drugs had opposite effects on locomotion. Thus iloperidon seems to possess superior effects compared to nemonaprid in schizophrenic patients with mood disorders.