Evaluation of the efficacy of antipsychotic attenuation of phencyclidine-disrupted prepulse inhibition in rats.
Phencyclidine reliably disrupts prepulse inhibition of the acoustic startle response in rats. Previous research has suggested that atypical antipsychotics (e.g., those that do not produce extrapyramidal motor effects) attenuate the disruptive effects of phencyclidine in this model whereas typical antipsychotics do not. Nearly all of this research has used the D2 antagonist haloperidol for comparison. In this study, antipsychotics with more diverse receptor binding profiles were tested for their efficacy in attenuating phencyclidine-induced disruption of prepulse inhibition. Results showed that phencyclidine disrupted prepulse inhibition in all groups of rats. Olanzapine, but not clozapine, attenuated this disruption, but this effect occurred only at a single (5 mg/kg) dose. None of the other antipsychotics nor spermine altered phencyclidine's effects. These results suggest that this model does not reliably differentiate between typical and atypical antipsychotics.
Wiley
J L
JL
Department of Pharmacology, Virginia Commonwealth University, Richmond 23298-0613, USA. jwiley@hsc.vcu.edu
Kennedy
K L
KL
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000706:statistics & numerical data; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D010622:Phencyclidine