Differential effects of antipsychotic and propsychotic drugs on prepulse inhibition and locomotor activity in Roman high- (RHA) and low-avoidance (RLA) rats

Ignasi Oliveras, Ana Sánchez-González, Daniel Sampedro-Viana, Maria Antonietta Piludu, Cristóbal Río-Alamos, Osvaldo Giorgi, Maria G. Corda, Susana Aznar, Javier González-Maeso, Cristina Gerbolés, Gloria Blázquez, Toni Cañete, Adolf Tobeña, Alberto Fernández-Teruel

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5 Citations (Scopus)

Abstract

© 2017, Springer-Verlag Berlin Heidelberg. Rationale: Animal models with predictive and construct validity are necessary for developing novel and efficient therapeutics for psychiatric disorders. Objectives: We have carried out a pharmacological characterization of the Roman high- (RHA-I) and low-avoidance (RLA-I) rat strains with different acutely administered propsychotic (DOI, MK-801) and antipsychotic drugs (haloperidol, clozapine), as well as apomorphine, on prepulse inhibition (PPI) of startle and locomotor activity (activity cages). Results: RHA-I rats display a consistent deficit of PPI compared with RLA-I rats. The typical antipsychotic haloperidol (dopamine D2 receptor antagonist) reversed the PPI deficit characteristic of RHA-I rats (in particular at 65 and 70 dB prepulse intensities) and reduced locomotion in both strains. The atypical antipsychotic clozapine (serotonin/dopamine receptor antagonist) did not affect PPI in either strain, but decreased locomotion in a dose-dependent manner in both rat strains. The mixed dopamine D1/D2 agonist, apomorphine, at the dose of 0.05 mg/kg, decreased PPI in RHA-I, but not RLA-I rats. The hallucinogen drug DOI (5-HT2A agonist; 0.1–1.0 mg/kg) disrupted PPI in RLA-I rats in a dose-dependent manner at the 70 dB prepulse intensity, while in RHA-I rats, only the 0.5 mg/kg dose impaired PPI at the 80 dB prepulse intensity. DOI slightly decreased locomotion in both strains. Finally, clozapine attenuated the PPI impairment induced by the NMDA receptor antagonist MK-801 only in RLA-I rats. Conclusions: These results add experimental evidence to the view that RHA-I rats represent a model with predictive and construct validity of some dopamine and 5-HT2A receptor-related features of schizophrenia.
Original languageEnglish
Pages (from-to)957-975
JournalPsychopharmacology
Volume234
Issue number6
DOIs
Publication statusPublished - 1 Mar 2017

Keywords

  • Activity
  • Antipsychotic drugs
  • Genetically based rat model
  • Predictive validity
  • Prepulse inhibition
  • Propsychotic drugs
  • Roman high- and low-avoidance rats
  • Schizophrenia

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