Inhibition of CB1 receptor ameliorates spatial learning and memory impairment in mice with traumatic brain injury

Traumatic brain injury (TBI) is an increasingly prevalent condition affecting people of all ages and genders. The impairment of spatial learning and memory is one of the most common effects of TBI. Unfortunately, it currently lacks effective therapeutic interventions. The endocannabinoid (EC) system regulates a diverse array of physiological processes. Here, we found a 6.7-fold increase of 2-AG levels at 1 d post-TBI, declining thereafter. After 5 d, the levels were still 3.3-fold higher than in the controls. AM281, a CB1 receptor antagonist, reversed the TBI-reduced NMDA receptor subunits NR2B in the hippocampus and ameliorate the spatial learning and memory impairment at 7 d post-TBI, suggesting CB1 receptor is involved in the TBI-induced hippocampal-dependent spatial learning and memory impairment.