The novel atypical antipsychotic olanzapine, but not the CCK-B antagonist LY288513, blocks apomorphine-induced disruption of pre-pulse inhibition.
Pre-pulse inhibition (PPI) of the acoustic startle response is the diminution of the startle response when the startle stimulus is preceded by a weaker, non-startle-eliciting stimulus. Deficits in PPI occur in animals following the administration of apomorphine and in schizophrenic patients. In this study, we examined the ability of the novel atypical antipsychotic olanzapine and the cholecystokinin (CCK)-B antagonist LY288513 to reverse the apomorphine-induced disruption of pre-pulse inhibition. Olanzapine (3.0 and 5.0 mg/kg, i.p.), but not LY288513 (1.0-100 mg/kg, p.o.), blocked apomorphine-induced disruption of PPI. These results indicate that olanzapine, but not LY288513, has dopamine antagonist properties in vivo and predict that olanzapine, but not LY288513, will have antipsychotic activity in man.
Rasmussen
K
K
Lilly Research Laboratories, Eli Lilly and Co., IN 46285, USA. rasmussen_kurt@lilly.com
Gates
M R
MR
Burger
J E
JE
Czachura
J F
JF
D000161:Acoustic Stimulation; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D001569:Benzodiazepines; D004305:Dose-Response Relationship, Drug; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects*
D014150:Antipsychotic Agents; D006727:Hormone Antagonists; D011720:Pyrazoles; D001569:Benzodiazepines; C074681:1-(4-bromophenylaminocarbonyl)-4,5-diphenyl-3-pyrazolidinone; D010890:Pirenzepine; D001058:Apomorphine; D000077152:Olanzapine