The atypical antipsychotic,aripiprazole, blocks phencyclidine-induced disruption of prepulse inhibition in mice |
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Authors: | Kim Fejgin Sergej Safonov Erik Pålsson Caroline Wass Jörgen A Engel Lennart Svensson Daniel Klamer |
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Institution: | 1.Institute of Neuroscience and Physiology, Department of Pharmacology, The Sahlgrenska Academy,G?teborg University,G?teborg,Sweden |
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Abstract: | Rationale 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. |
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Keywords: | Prepulse inhibition Antipsychotic Schizophrenia Phencyclidine Mouse |
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