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Evaluating the effects of 2-BFI and tracizoline, two potent I2-imidazoline receptor agonists, on cognitive performance and affect in middle-aged rats

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Abstract

Cognitive performance and affective-like responses are particularly susceptible to decline during the aging process. Since imidazoline receptors I2 are altered in neurodegenerative and psychiatric disorders, the pharmacological modulation of I2 receptors could be of potential interest to improve these age-related behavioral deficits. In this context, the present study explored the potential pro-cognitive as well as antidepressant-like effects of two potent I2 agonists, 2-BFI (2-(2-benzofuranyl)-2-imidazoline), and tracizoline (2-styryl-4,5-dihydro-lH-imidazole, also known as LSL 61122 or valldemossine) in middle-aged male rats. Following a preliminary study performed to select a dose regimen capable of inducing neuroplastic events (i.e., regulation of hippocampal FADD cell fate adaptor), 2-BFI or tracizoline (10 mg/kg, i.p.) was administered to 9–10-month-old Sprague-Dawley rats. Cognitive performance was evaluated in the 8-arm radial maze and antidepressant-like responses under the stress of the forced-swim test. At the dose selected, 2-BFI and tracizoline did not alter body weight or cognitive performance. Interestingly, 2-BFI (but not tracizoline) induced hypothermia over the course of treatment and an antidepressant-like response in the forced-swim test. These compounds did not improve cognitive performance in middle-aged rats; however, 2-BFI exerted an antidepressant-like response. These results are in line with prior reports suggesting a beneficial impact induced by certain I2 ligands on affective-like behavior, while adding that the beneficial effects were mediated by increasing climbing behavior and with the novelty and importance of demonstrating this effect for middle-aged rats.

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Acknowledgments

The authors thank Dr Rossend Obach and Dr Ángel Menargues (LASA Laboratorios and later Ipsen Pharma SA, Barcelona, Spain) for initially providing the compounds 2-BFI and LSL 61122 (tracizoline, valldemossine) to Dr Jesús A. García-Sevilla who kindly gave a sample of each for the present experiments. The authors also thank Sandra Ledesma-Corvi who helped with procedural assistance.

Funding

EH-H is supported by a predoctoral scholarship (FPI/2102/2018; Consejería de Innovación, Investigación y Turismo del Gobierno de las Islas Baleares y del Fondo Social Europeo).

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Authors and Affiliations

  1. IUNICS, University of the Balearic Islands, Cra. Valldemossa km 7.5, E-07122, Palma, Spain

    Elena Hernández-Hernández & M. Julia García-Fuster

  2. Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain

    Elena Hernández-Hernández & M. Julia García-Fuster

Authors
  1. Elena Hernández-Hernández
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  2. M. Julia García-Fuster
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Contributions

EH-H and MJG-F designed the study. EH-H performed the behavioral testing and analysis. MJG-F wrote the first draft of the manuscript. Both authors contributed to and approved the final version of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to M. Julia García-Fuster.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All animal experiments adhered to ethical standards. The care of animals was performed following the ARRIVE guidelines (McGrath and Lilley, 2015) in accordance with the UK Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/63/EU, under which the study was performed, and were approved by the Local Bioethical Committee (University of the Balearic Islands) and the regional Government (Conselleria Medi Ambient, Agricultura i Pesca, Direcció General Agricultura i Ramaderia, Govern de les Illes Balears). All efforts were made to minimize the number of rats used and their suffering.

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Hernández-Hernández, E., García-Fuster, M.J. Evaluating the effects of 2-BFI and tracizoline, two potent I2-imidazoline receptor agonists, on cognitive performance and affect in middle-aged rats. Naunyn-Schmiedeberg's Arch Pharmacol 394, 989–996 (2021). https://doi.org/10.1007/s00210-020-02042-6

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  • DOI: https://doi.org/10.1007/s00210-020-02042-6

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