Evaluating the effects of 2-BFI and tracizoline, two potent I₂-imidazoline receptor agonists, on cognitive...

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.