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

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.