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KMID : 0361520080190010038
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Korean Journal of Psychopharmacology
2008 Volume.19 No. 1 p.38 ~ p.45
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Effects of a New Antipsychotic Drug (YKP1447) on Impaired Prepulse Inhibition Induced by Apomorphine and Phencyclidine in Rats
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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 Young-Gil
Kwak Byong-Sung
Choi Jung-Sesk
Kim Hyun-Taek
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Abstract
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Objectives :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 ㎎/㎏) or vehicle (VEH) was administered 15 min before the injection of APO (0.5 ㎎/㎏, Exp1) or PCP (2.0 ㎎/㎏, Exp2：1.5 ㎎/㎏, 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 ㎎/㎏) (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.
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KEYWORD
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Apomorphine, Phencyclidine, New antipsychotic drug(YKP1447), Prepulse inhibition
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