4.7 Article

Iloperidone reduces sensorimotor gating deficits in pharmacological models, but not a developmental model, of disrupted prepulse inhibition in rats

期刊

NEUROPHARMACOLOGY
卷 51, 期 3, 页码 457-465

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2006.04.004

关键词

animal model; atypical antipsychotic; isolation rearing; prepulse inhibition; psychosis; schizophrenia

资金

  1. NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH042228, R01MH052885, R01MH062527] Funding Source: NIH RePORTER
  2. NIMH NIH HHS [R01 MH52885, R01 MH62527, R01 MH42228] Funding Source: Medline

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Iloperidone is a novel atypical antipsychotic which acts as a broad spectrum dopamine/serotonin/norepinephrine receptor antagonist. To compare iloperidone behaviorally to other known antipsychotics, we evaluated the drug in three pharmacological models and one developmental model of disrupted prepulse inhibition (PPI) in rats. Firstly, 0.5 mg/kg apomorphine induced PPI deficits that were prevented by pretreatment with iloperidone (I and 3 mg/kg). Secondly, treatment with the N-methyl-D-aspartate (NMDA)-receptor antagonist phencyclidine (PCP) produced robust deficits in PPI. Both doses of iloperidone (I and 3 mg/kg) prevented the PPI-disruptive effects of treatment with I mg/kg PCP. Thirdly, treatment with the alpha(1)-adrenoceptor agonist cirazoline (0.6 mg/kg) disrupted PPI, and produced a concurrent large increase in startle magnitude. A relatively low dose of iloperidone (0.3 mg/kg) prevented cirazoline-induced PPI deficits, independent of its effects on startle magnitude. Finally, iloperidone (I mg/kg) did not reverse PPI deficits in the isolation-rearing model of schizophrenia. These results indicate that iloperidone exerts behavioral effects in pharmacological models of disrupted sensorimotor gating consistent with. atypical antipsychotics, mediated by antagonism of dopaminergic and noradrenergic receptors. The absence of effect in isolation-reared rats may be due to the relatively small effect size of isolation rearing on PPI or dose of iloperidone. (c) 2006 Elsevier Ltd. All rights reserved.

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