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Exploring the antidepressant-like potential of the selective I2-imidazoline receptor ligand LSL 60101 in adult male rats

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Abstract

Background

While the alteration of I2 receptors has been associated with neurodegenerative and psychiatric disorders, among other brain dysfunctions, I2 selective agonists are also capable of inducing analgesia in models of chronic pain, improving cognition and inducing hypothermia and neuroprotection. However, the literature evaluating the antidepressant-like potential of I2 ligands is scarce and showed mixed results, whereas some studies reported antidepressant-like effects for certain I2 ligands others denied them. In this context, we evaluated the antidepressant-like potential of a highly selective I2-receptor ligand, LSL 60101 ([2-(2-benzofuranyl)-2-imidazole]).

Methods

LSL 60101 was administered in adult male Sprague–Dawley rats daily during 16 days (doses of 10 and 20 mg/kg, ip) and its antidepressant-like potential was assessed through the course of treatment in the forced-swim test, novelty-suppressed feeding test and two-bottle choice test (sucrose preference). The regulation of several key neuroplasticity markers (i.e., FADD, p-ERK1/2, ERK1/2, p-JNK1/2, JNK1/2, mBDNF) was evaluated 24-h post-treatment by western blot analysis in the right hippocampus and the proliferation of neural progenitors was quantified in the left hippocampus by immunohistochemistry.

Results

The results showed that LSL 60101 did not induce an antidepressant-like effect over the course of treatment in any of the behavioral tests conducted, and it did not alter any of the hippocampal neuroplasticity markers evaluated.

Conclusion

These results add to the existing literature by suggesting that not all I2 ligands might be capable of displaying an antidepressant-like potential, and that particularities in the chemical structure of each compound might help explain these discrepancies and deserve future studies.

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Acknowledgements

The authors thank Dr. Rossend Obach and Dr. Ángel Menargues (LASA Laboratorios and later Ipsen Pharma SA, Barcelona, Spain) for initially providing the compound LSL 60101 (see [11]), and Dr. Carmen Escolano (Medicinal Chemistry, School of Pharmacy, University of Barcelona) for retesting LSL 60101 structural integrity.

Funding

This research was not financed by any particular grant. EH-H is supported by a predoctoral fellowship (Consejería de Innovación, Investigación y Turismo del Gobierno de las Islas Baleares y del Fondo Social Europeo, FPI/2102/2018).

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Authors and Affiliations

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

    Elena Hernández-Hernández, Jesús A. García-Sevilla & M. Julia García-Fuster

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

    Elena Hernández-Hernández, Jesús A. García-Sevilla & M. Julia García-Fuster

Authors
  1. Elena Hernández-Hernández
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  2. Jesús A. García-Sevilla
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  3. M. Julia García-Fuster
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Contributions

EH-H and MJG-F were responsible for the study concept and design. EH-H conducted the experiments and analyzed the behavioral and molecular data. EH-H and MJG-F wrote the first draft of the manuscript. JAG-S critically revised the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to M. Julia García-Fuster.

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Hernández-Hernández, E., García-Sevilla, J.A. & García-Fuster, M.J. Exploring the antidepressant-like potential of the selective I2-imidazoline receptor ligand LSL 60101 in adult male rats. Pharmacol. Rep 73, 288–295 (2021). https://doi.org/10.1007/s43440-020-00148-5

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  • DOI: https://doi.org/10.1007/s43440-020-00148-5

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