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

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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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Acknowledgement

This study was supported by grants from the Swedish Medical Research Council (4247), the Theodore and Vada Stanley Foundation, Magnus Bergvalls Stiftelse, Stiftelsen Clas Groschinskys Minnesfond, Göteborgs Läkaresällskap, Wilhelm och Martina Lundgrens Vetenskapsfond, Stiftelsen Bengt Dahréns fond, the Swedish Society of Medicine, Åke Wibergs Stiftelse, Adlerbertska Forskningsstiftelsen, Fredrik och Ingrid Thurings Stiftelse, Åhlén-Stiftelsen and Svenska Lundbeckstiftelsen. Aripiprazole was generously supplied by Bristol-Myers Squibb, Sweden.

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Authors and Affiliations

  1. Institute of Neuroscience and Physiology, Department of Pharmacology, The Sahlgrenska Academy, Göteborg University, P.O. Box 431, SE 405 30, Göteborg, Sweden

    Kim Fejgin, Sergej Safonov, Erik Pålsson, Caroline Wass, Jörgen A. Engel, Lennart Svensson & Daniel Klamer

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  1. Kim Fejgin
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  2. Sergej Safonov
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  3. Erik Pålsson
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  4. Caroline Wass
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  5. Jörgen A. Engel
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  6. Lennart Svensson
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  7. Daniel Klamer
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Corresponding author

Correspondence to Lennart Svensson.

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Fejgin, K., Safonov, S., Pålsson, E. et al. The atypical antipsychotic, aripiprazole, blocks phencyclidine-induced disruption of prepulse inhibition in mice. Psychopharmacology 191, 377–385 (2007). https://doi.org/10.1007/s00213-006-0658-y

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  • DOI: https://doi.org/10.1007/s00213-006-0658-y

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