Subchronic effects of ligands of cannabinoid receptors on learning and memory processes of olfactory bulbectomized rats

The brain endocannabinoid system has been shown to play a role in many physiological processes, including mood, learning and memory. It is also involved in the pathogenesis of anxiety, depression, mood disorders, as well as neurodegenerative disorders, although the exact mechanisms by which cannabinoid receptors interfere in these disorders are not well established. The aim of the present study was to evaluate the effects of cannabinoid ligands HU-210 (CB1 receptor agonist) and SR 141716A (CB1 receptor antagonist) on learning and memory processes of rats with depressive - like state, induced by bilateral olfactory bulbectomy. The bilateral olfactory bulbectomy (OBX) is a validated model of depression, which can be used also as an animal model of Alzheimer's disease. We found that the subchronic treatment of OBX rats with HU 210 and SR 141716A exerted modulatory effect on rat's performance in both active avoidance (shuttle box) and passive avoidance (step through) tests. HU 210 ameliorated the memory deficits of OBX rats; however, the scores of the sham-operated controls had not been reached. SR 141716A modified the avoidance performance in OBX rats and showed a memory enhancing effect in the sham-operated rats. Our findings suggest that CB1 receptors might be involved in avoidance learning and memory acquisition in OBX rats.