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.
Hernández-Hernández, E., García-Sevilla, J. A., & García-Fuster, M. J. (2020). Exploring the antidepressant-like potential of the selective I2-imidazoline receptor ligand LSL 60101 in adult male rats. Pharmacological Reports. https://doi.org/10.1007/s43440-020-00148-5