Effects of a New Antipsychotic Drug (YKP1447) on Impaired Prepulse Inhibition Induced by Apomorphine and Phencyclidine in Rats

Yoon, Byung Soo; Park, Eun Hye; Park, Eui Ho; Kwon, Jeong Tae; Hong, Sung Bin; Dong, Seon Min; Kim, Yun Hee; Heo, Joon; Ji, Mi Kyung; Kim, Yong Gil; Kwak, Byong Sung; Choi, June Seek; Kim, Hyun Taek

Abstract

OBJECTIVE
Schizophrenia, a devastating mental disorder, displays a wide range of cognitive impairments including attentional impairment. Prepulse inhibition (PPI), in which a startle response to a loud acoustic noise is reduced by a preceding auditory stimulus of a lower intensity, is impaired in schizophrenic patients and rats injected with apomorphine (APO) or phencyclidine (PCP) mimicking attentional deficits in schizophrenics. Here we examined therapeutic efficacy of a newly developed atypical antipsychotic compound (YKP1447;YKP) on PPI impairment induced by various doses of APO and PCP.
METHODS
This study was composed of 3 experiments. YKP (0.5-15 mg/kg) or vehicle (VEH) was administered 15 min before the injection of APO (0.5 mg/kg, Exp1) or PCP (2.0 mg/kg, Exp2:1.5 mg/kg, Exp3). They were then tested for PPI in which a mix of startle stimulus and prepulse was presented.
RESULTS
APO or PCP treatment effectively impaired PPI in tested animals (VEH/APO or VEH/PCP). Impaired PPI in APO group was reversed in animals that were pretreated with YKP (5-10 mg/kg) (Exp1). However YKP treatment was not effective in PCP group (Exp2-3).
CONCLUSION
High concentration of YKP pretreatment had antipsychotic effect on APO-induced impairment in attentional function suggesting that the compound could potentially be used to treat cognitive impairment due to increased dopaminergic receptorbinding.