The Action of TAAR1 Agonist RO5263397 on Executive Functions in Rats

Abstract

Trace amine-associated receptor 1 (TAAR1) is a widely recognized new perspective target for the neuropsychiatric pharmacological treatment. Despite a growing number of studies investigating TAAR1 role in the animal models of different pathologies, information of TAAR1 agonists impact on executive cognitive functions is limited. The goal of the present study was to evaluate the activity of highly selective partial TAAR1 agonist RO5263397 on various executive cognitive functions. The results of the present study demonstrated that the pretreatment with RO5263397 was able to increase attention and decrease cognitive flexibility in rats. The analysis of the RO5263397 action on impulsivity demonstrated that the TAAR1 activation failed to affect premature responding but was able to slightly modify impulsive choice. Problem solving was resistant to the pharmacological intervention.

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Acknowledgements

First of all, the authors would like to thank Dr Marius C. Hoener (F. Hoffmann-La Roche, Basel, Switzerland) for generous gift of compound RO5263397, Dr Mariia Dorofeikova for help in performing of OPBRS experiment, Dr Alexey I. Nevorotin, Dr Alexander Zhivich and Victor Zhivich for editing the manuscript as well as Dr Anton Bespalov for precious advices on the structure of Discussion section. The preliminary results of this study were presented at the 31st European College of Neuropsychopharmacology (ECNP) Congress (October 6–9, 2018, Barcelona, Spain) and published as the conference abstract in European Neuropsychopharmacology (2019, 29 (1S): S261–S262).

Funding

This study was supported by the Russian Science Foundation (Grant #17-75-20177).

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Authors

Contributions

IS, RRG, EEZ designed and directed the project. MT, ADor, ADol, and NB performed the experiments. IS, MT and IVB analyzed the data. All authors discussed the results and contributed to the final manuscript. IS wrote the manuscript.

Corresponding author

Correspondence to Ilya Sukhanov.

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All authors declared that they have no conflict of interest.

Ethical Approval

The First Pavlov State Saint Petersburg Medical University guideline for the care and use of animals was followed. Experimental protocols were approved by the Local Animal Care and Use Committee of First Pavlov State Saint Petersburg Medical University.

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Chemical Compounds Studied in This Article: RO5263397.

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Dorotenko, A., Tur, M., Dolgorukova, A. et al. The Action of TAAR1 Agonist RO5263397 on Executive Functions in Rats. Cell Mol Neurobiol 40, 215–228 (2020). https://doi.org/10.1007/s10571-019-00757-6

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Keywords

  • TAAR1
  • RO5263397
  • Attention
  • Impulsivity
  • Cognitive flexibility
  • Rats