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

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Abstract

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.

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Abbreviations

PPI:

Prepulse inhibition

RLA:

Roman high-avoidance

RHA:

Roman low-avoidance

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Acknowledgements

This work was supported by grants PSI2013-41872-P (MINECO), 2014SGR-1587 (DGR), “ICREA-Academia 2013” to AF-T and by a grant from the Regional Government of Sardinia (RAS) (L.R.7/2007, Project code no. CRP-59842) to OG. IO is recipient of a PhD FI fellowship (DGR 2014). AS-G is recipient of a PhD FPI fellowship. MAP is a recipient of a PhD fellowship from RAS.

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Authors and Affiliations

  1. Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, Universidad Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain

    Ignasi Oliveras, Ana Sánchez-González, Daniel Sampedro-Viana, Cristóbal Río-Alamos, Cristina Gerbolés, Gloria Blázquez, Toni Cañete, Adolf Tobeña & Alberto Fernández-Teruel

  2. Department of Life and Environmental Sciences, Section of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, 09124, Cagliari, Italy

    Maria Antonietta Piludu, Osvaldo Giorgi & Maria G. Corda

  3. Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Copenhagen, Denmark

    Susana Aznar

  4. Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, 23298, USA

    Javier González-Maeso

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  1. Ignasi Oliveras
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  2. Ana Sánchez-González
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  14. Alberto Fernández-Teruel
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Correspondence to Alberto Fernández-Teruel.

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Oliveras, I., Sánchez-González, A., Sampedro-Viana, D. et al. Differential effects of antipsychotic and propsychotic drugs on prepulse inhibition and locomotor activity in Roman high- (RHA) and low-avoidance (RLA) rats. Psychopharmacology 234, 957–975 (2017). https://doi.org/10.1007/s00213-017-4534-8

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  • DOI: https://doi.org/10.1007/s00213-017-4534-8

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