title: The atypical antipsychotic, aripiprazole, blocks phencyclidine-induced disruption of prepulse inhibition in mice.
abstract: BACKGROUND
  The psychotomimetic drug, phencyclidine, induces schizophrenia-like behavioural changes in both humans and animals. Phencyclidine-induced disruption of sensory motor gating mechanisms, as assessed by prepulse inhibition of the acoustic startle, is widely used in research animals as a screening model for antipsychotic properties in general and may predict effects on negative and cognitive deficits in particular. Dopamine (DA) stabilizers comprise a new generation of antipsychotics characterized by a partial DA receptor agonist or antagonist action and have been suggested to have a more favourable clinical profile.
  
  
  OBJECTIVE
  The aim of the present study was to investigate the ability of first, second and third generation antipsychotics to interfere with the disruptive effect of phencyclidine on prepulse inhibition in mice.
  
  
  RESULTS
  Aripiprazole blocked the phencyclidine-induced disruption of prepulse inhibition. The atypical antipsychotic clozapine was less effective, whereas olanzapine, and the typical antipsychotic haloperidol, failed to alter the effects of phencyclidine on prepulse inhibition.
  
  
  CONCLUSIONS
  The somewhat superior efficacy of clozapine compared to haloperidol may be explained by its lower affinity and faster dissociation rate for DA D2 receptors possibly combined with an interaction with other receptor systems. Aripiprazole was found to be more effective than clozapine or olanzapine, which may be explained by a partial agonist activity of aripiprazole at DA D2 receptors. In conclusion, the present findings suggest that partial DA agonism leading to DA stabilizing properties may have favourable effects on sensorimotor gating and thus tentatively on cognitive dysfunctions in schizophrenia.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Pharmacology, The Sahlgrenska Academy, Göteborg University, P.O. Box 431, SE 405 30, Göteborg, Sweden.
authors.forename: Kim
authors.initials: K
authors.lastname: Fejgin
authors.forename: Sergej
authors.initials: S
authors.lastname: Safonov
authors.forename: Erik
authors.initials: E
authors.lastname: Pålsson
authors.forename: Caroline
authors.initials: C
authors.lastname: Wass
authors.forename: Jörgen A
authors.initials: JA
authors.lastname: Engel
authors.forename: Lennart
authors.initials: L
authors.lastname: Svensson
authors.forename: Daniel
authors.initials: D
authors.lastname: Klamer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects*; D000077152:Olanzapine; D010622:Phencyclidine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013216:Reflex, Startle / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D000068180:Aripiprazole; D010622:Phencyclidine; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine