The atypical antipsychotic, aripiprazole, blocks phencyclidine-induced disruption of prepulse inhibition in mice

• Published in: Psychopharmacologia Vol. 191; no. 2; pp. 377 - 385
• Main Authors: FEJGIN, Kim, SAFONOV, Sergej, PALSSON, Erik, WASS, Caroline, ENGEL, Jörgen A, SVENSSON, Lennart, KLAMER, Daniel
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.04.2007; Springer Nature B.V
• Subjects: Adult and adolescent clinical studies; agonists; Analysis of Variance; Animal; Animals; Antipsychotic Agents; Antipsychotic Agents - pharmacology; Aripiprazole; Behavior; Behavior, Animal - drug effects; Benzodiazepines; Benzodiazepines - pharmacology; Biological and medical sciences; Clozapine; Clozapine - pharmacology; Cognition & reasoning; Dopamine D2; Dose-Response Relationship; Dose-Response Relationship, Drug; Drug; drug effects; drug therapy; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Antagonists - pharmacology; Farmakologi och toxikologi; Haloperidol; Haloperidol - pharmacology; Inhibitor drugs; Male; Medical sciences; Mice; Neural Inhibition; Neural Inhibition - drug effects; Neuropharmacology; Pharmacology; Pharmacology and Toxicology; Pharmacology. Drug treatments; Phencyclidine; Phencyclidine - pharmacology; Piperazines; Piperazines - pharmacology; Psycholeptics: tranquillizer, neuroleptic; Psychology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Quinolones; Quinolones - pharmacology; Receptors; Receptors, Dopamine D2 - agonists; Reflex, Startle - drug effects; Rodents; Schizophrenia; Schizophrenia - drug therapy; Startle Reaction; Partial agonist; Atypical antipsychotic; Neuroleptic; Psychotropic; Schizophrenia; Glutamate receptor; Aripiprazole; Psychosis; 5-HT1A Serotonine receptor; Phencyclidine; Piperidine derivatives; Hallucinogen; Antipsychotic; Drug of abuse; Antagonist; 5-HT2A serotonin receptor; Rodentia; Neuroprotective agent; Vertebrata; Chemotherapy; Mammalia; D2 Dopamine receptor; Treatment; Mouse; Animal; NMDA receptor; Prepulse inhibition
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-006-0658-y

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. 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. 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. 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.