WIN55,212-2 impairs non-associative recognition and spatial memory in rats via CB1 receptor stimulation

Endogenous and exogenous cannabinoids modulate learning and memory primarily via the cannabinoid type 1 receptor (CB1R). A variety of experimental procedures has focused on the role of CB1R in various aspects of learning and memory processes. However, the picture still remains unclear as there is a lack of information on the effects of relatively low doses of CB1R agonists in relation to their effects on locomotion. The present study sought to investigate CB1R activation, using a range of relatively low doses of the CB1R agonist WIN55,212-2, on multiple aspects of learning and memory in rats. For this purpose, non-associative learning was examined using the habituation of locomotion paradigm, recognition memory was evaluated with the novel object recognition task, and the radial water maze test was selected to assess rats' spatial memory. The ability of the CB1R antagonist, SR141716A, to counteract WIN55,212-2-induced behavioral effects was also tested. WIN55,212-2 (0.3, but not 0.03 or 0.1 mg/kg) disrupted non-associative learning, different aspects of short- and long-term recognition memory (storage and retrieval) and retention of spatial memory. The 0.3 mg/kg dose of WIN55,212-2 also decreased ambulatory, but not vertical (rearing), activity in non-habituated rats. These effects appeared to be CB1R dependent since pretreatment with SR141716A (0.03 mg/kg) prevented the WIN55,212-2-induced behavioral effects. The present findings further support and extend the complex impact of exogenous cannabinoids on learning and memory in relation to their effects on locomotion.