Genetic and pharmacological approaches to evaluate the interaction between the cannabinoid and cholinergic systems in cognitive processes

Background and purpose: The objective of this study was to investigate the possible interactions between the cannabinoid and cholinergic systems in memory and learning processes by using genetic and pharmacological approaches in two different behavioural models, the active avoidance and the object recognition test. Experimental approach: The effects induced by nicotine, physostigmine and scopolamine were studied in CB1 receptor knockout and wild- type mice in the active avoidance paradigm. In addition, the effects of pretreatment with the CB1 receptor antagonist rimonabant were evaluated on the responses induced by nicotine in the active avoidance and the object recognition tasks in wild- type mice. Key results: Nicotine ( 0.5 mgkg(-1) s.c.) did not modify the performance of CB1 knockout and wild- type mice in this model, whereas scopolamine ( 0.5 mgkg(-1) i. p.) impaired the performance in both genotypes. Physostigmine ( 0.1 mgkg(-1) i. p.) increased the active avoidance performance in wild- type but not in CB1 knockout mice. Rimonabant ( 0.3, 1, 3, and 10 mgkg(-1)) did not modify the performance in the active avoidance test, given alone or co- administered with nicotine. In contrast, nicotine enhanced the performance in the object recognition task but this response was attenuated by rimonabant co-administration. Conclusions and implications: The present findings revealed that the cognitive effects of nicotine and physostigmine were attenuated in the absence of CB1 receptor activity. Scopolamine effects were independent from CB1 receptors.