The effect of aripiprazole on prepulse inhibition of the startle response in normal and hyperdopaminergic states in rats.
This study compared the D(2) partial agonists, aripiprazole, (R(+)-terguride; S(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine [S(-)-3-PPP]; 7-[3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy]-2(1H)-quinolinone [OPC-4392]) and D(2) antagonists (haloperidol, olanzapine, clozapine, risperidone, and quetiapine) on prepulse inhibition (PPI) of the startle response, and the ability to reverse apomorphine-induced deficits in the PPI response. Aripiprazole did not essentially affect PPI in naïve rats but dose-dependently restored apomorphine-induced PPI disruption. R(+)-terguride restored PPI disruption but suppressed PPI significantly in naïve rats, S(-)-3-PPP partially restored whereas OPC-4392 did not restore PPI disruption. Haloperidol and risperidone restored PPI disruption whereas olanzapine and quetiapine partially restored PPI disruption and clozapine had no restorative effect. In conclusion, aripiprazole, unlike other antipsychotic agents, failed to suppress PPI significantly and restored PPI disruption.
Second Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Kagasuno, Kawauchi-cho, Tokushima, Japan. s_nakai@research.otsuka.co.jp
Satoru
S
Nakai
Tsuyoshi
T
Hirose
Toyoki
T
Mori
Arlene
A
Stark
Hiroaki
H
Araki
Tetsuro
T
Kikuchi
D000161:Acoustic Stimulation; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D000068180:Aripiprazole; D003214:Conditioning, Classical / Q000187:drug effects; D015259:Dopamine Agents / Q000145:classification / Q000494:pharmacology*; D004347:Drug Interactions; D007266:Inhibition, Psychological; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects*
D014150:Antipsychotic Agents; D015259:Dopamine Agents; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D000068180:Aripiprazole; D001058:Apomorphine