Inhibition of CB1 receptor alleviates electroconvulsive shock-induced memory impairment by regulating hippocampal synaptic plasticity in depressive rats.

Electroconvulsive therapy (ECT) is one of the most effective treatments for depression, but it can cause cognitive deficit. Unfortunately, effective preventive measures are still lacking. The endocannabinoid system is thought to play a key role in regulation of cognitive process. Whether the endocannabinoid system is involved in the learning and memory impairment caused by ECS remain unclear. In this work, we first found that cannabinoid receptor type 1 (CB1R) and 2-arachidonoylglycerol (2-AG) were strongly expressed in hippocampus by electroconvulsive shock (ECS) in a rat depression model established by chronic mild stress (CMS). Pharmacological inhibition of CB1R using AM251 in vivo resulted in a pronounced relief in ECS-induced spatial learning and memory impairment as well as in a marked reversal of impaired hippocampal long-term potentiation (LTP), and reduced synapse-related proteins expression. Furthermore, results of sucrose preference test (SPT) and open-field test (OFT) showed that AM251 had no significant impact on the therapeutic effects of ECS on pleasure and psychomotor activity. Taken together, we identified that CB1R is involved in the ECS-induced spatial learning and memory impairment and Inhibition of CB1R facilitates the recovery of memory impairment and hippocampal synaptic plasticity, without interfering with the therapeutic effects of ECS in depressed rats.