Abstract
Mild traumatic brain injuries are common and can lead to memory deficits, partly due to hippocampal dysfunction. Mild traumatic brain injury causes a decrease in network excitability in area CA1 of the hippocampus. We have previously demonstrated that applying the cannabinoid receptor agonist WIN55,212-2 to injured brain slices, restores action potential firing to levels not significantly different than action potentials recorded in slices from uninjured (sham) animals. Here, we evaluated whether WIN55,212-2 also improves hippocampal-dependent memory in vivo using a contextual fear conditioning paradigm. Mice subjected to lateral fluid percussion injury were treated with WIN55,212-2 at doses of 0.75, 0.25, or 0.1mg/kg. Memory is thought to consist of three components: encoding (conditioning), consolidation, and retrieval (testing). At 0.75mg/kg and 0.25mg/kg, all mice froze significantly more than control mice indicating that mouse locomotion was affected at those doses. At concentrations of 0.1mg/kg we observed that injured and sham mice showed no significant differences in freezing rate compared to control sham mice but froze significantly more than injured controls. When administered at 0.1mg/kg only on conditioning days, we saw a similar effect as when injected on both conditioning and testing days. These results suggest that WIN55,212-2 at 0.1 mg/kg primarily aids memory encoding rather than retrieval. Overall, the study demonstrates that at the 0.1mg/kg dose, WIN55,212-2 can restore hippocampal-dependent memory function in lateral fluid percussion injury mice, providing insights into the potential therapeutic role of cannabinoid receptor agonists in mitigating memory deficits following mild traumatic brain injury.