PM432. Evaluation of the extrapyramidal side effects (EPS) liability of NMDA receptor glycine-binding site agonists

s | 57 in mPFC and DA efflux in dSTR. NGB and Blo improved the scPCP-induced NOR deficit. The combination of SED NGB and Blon improved the NOR deficit. Conclusions: D3 receptor blockade may contribute to the ability of Blon to increase cortical ACh and DA efflux, as well as to restore NOR in scPCP deficit. D3 receptor blockade may be an important component of the efficacy of Blon to enhance neurotransmitter efflux and improve cognitive function. 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 Oguz Mutlu1, EsenGumuslu2, Guner Ulak1, Furuzan Akar1, Faruk Erden1, Ipek Komsuoglu Celikyurt 1, Pelin Tanyeri3 1Department of Medical Pharmacology, Medical Faculty, Kocaeli University, Kocaeli, Turkey 2Department of Medical Genetics, Medical Faculty, Kocaeli University, Kocaeli, Turkey. 3Department of Pharmacology, Medical Faculty, Sakarya University, Sakarya, Turkey 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.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. PM432 Evaluation of the extrapyramidal side effects (EPS) liability of NMDA receptor glycine-binding site agonists Yukihiro Ohno, Syodai Fujii, Akiyoshi Inada, Yuka Sato, Saki Shimizu, Syunsaku Sogabe, Haruna Takasaki, Ryo Wakamatsu, Megumi Yamanaka, Ryoto Yanagisako Osaka University of Pharmaceutical Sciences, Japan Abstract Glutamatergic system is implicated in pathogenesis of schizophrenia (Glutamate hypothesis) and stimulants for NMDA receptor glycine-binding sites are expected as novel medications for schizophrenia, especially for negative symptoms and cognitive impairments. However, the actions of NMDA receptor glycinebinding site agonists in modulating antipsychotic-induced EPS remain to be clarified. In this study, we examined the effects of the glycine-site agonists of NMDA receptors, D-cycloserine, D-serine and glycine on haloperidol-induced EPS (i.e., bradykinesia and catalepsy) in rodents. NMDA receptor glycine-binding site agonist, D-cycloserine (3–30 mg/kg, i.p.) significantly improved haloperidol (1 mg/kg, i.p.)-induced bradykinesia in a dose-dependent manner. D-serine (100–1000 mg/kg, i.p.) also reduced haloperidol-induced bradykinesia, but glycine (30–300 mg/kg, i.p.) did not. Attenuation of haloperidol-induced bradykinesia by D-cycloserine was reversed by the NMDA antagonist MK-801 or the NOS inhibitor L-NAME. In addition, microinjection of D-cycloserine (10 μg/μL/ side) into substantia nigra or dorsolateral striatum, both significantly attenuated the EPS induction. The present results indicates that activation of glycine-binding sites of NMDA receptors alleviates the antipsychotic-induced EPS, implying that the glycine-binding site agonists of NMDA receptors, like D-cycloserine, provide benefits not only for the efficacy, but also in terms of EPS induction in the treatment of schizophrenia. PM433 Prenatal risperidone exposure impaired cognitive function and enhances prepulse inhibition of acoustic startle reflex in adult male mice Yun-Ai Su, Ji-Tao Li, Tian-Mei Si, Han Wang Peking University, China Abstract Objective: Psychiatric disorders are relatively common among women of childbearing age. However, the use of antipsychotics during pregnancy remains controversial. Previous animal studies indicate that prenatal exposure to antipsychotics may impair the cognitive function of adult offspring. The current study investigated whether prenatal risperidone treatment would produce long-term effects on behavior in adult male offspring. Methods: All plug-positive female C57BL/6 mice were randomized two groups. Pregnant dams of both groups received aObjective: Psychiatric disorders are relatively common among women of childbearing age. However, the use of antipsychotics during pregnancy remains controversial. Previous animal studies indicate that prenatal exposure to antipsychotics may impair the cognitive function of adult offspring. The current study investigated whether prenatal risperidone treatment would produce long-term effects on behavior in adult male offspring. Methods: All plug-positive female C57BL/6 mice were randomized two groups. Pregnant dams of both groups received a daily intraperitoneal injection of risperidone (2mg/kg body weight) or vehicle from embryonic day 6 to 16. Pups were reared by their biological mothers. Experiment 1 examined the shortterm effects of prenatal risperidone on hippocampal synaptic protein expression levels of the male pups on P10. In experiment 2, mice were examined in the spontaneous locomotion, spatial object recognition, elevated plus maze and prepulse inhibition of acoustic startle reflex sequentially on P75. Results: The data showed no significant difference in the body weight of treated offspring as compared to those of the controls. The postsynaptic protein PSD-95 in the hippocampus of male pups was downregulated by prenatal risperidone exposure. The total distance traveled in the novel environment of the open field test did not reveal any differences between two groups. Male mice offspring exposed to risperidone showed deficits in novel object recognition when compared with control group. Prenatal risperidone treatment has no significant effects on anxietyrelated behavior in adult male offspring. However, the offspring of risperidone group showed significantly potentiated PPI. Conclusion: Prenatal exposure to risperidone during a critical period of brain development leaves a lasting imprint on the