The Effect of CB1r Hippocampal Activation on Behavioral Changes and BDNF Levels in Rapid-Eye Movement Sleep-Deprived Rats

Abstract

The endocannabinoid (eCB) system modulates cognitive and behavioral functions mainly via cannabinoid Type 1 receptor (CB1r). Rapid-eye movement (REM) sleep deprivation (SD) also affects behavioral functions. Importantly, there may be an interaction between CB1r function and REM SD effects; however, evidence is sparse. In the present research, we investigated the interaction effect of REM SD and CB1r on anxiety, depressive-like behavior, pain threshold, locomotor activity, and brain-derived neurotrophic factor (BDNF) in rats. Arachidonylcyclopropylamide (ACPA; 1, 3, and 5 ng/side), a CB1r agonist, was injected intra-CA1. REM SD was induced by the multiple platform apparatus for 48 h. The results showed that 48-h REM SD increased anxiety- and depressive-like behaviors and decreased locomotion, pain threshold, and BDNF hippocampal level. ACPA dose-dependently attenuated or restored these effects. ACPA (5 ng/side) also increased pain threshold in control and sham-REM SD rats and decreased locomotion in sham-REM SD rats. Pearson correlation test revealed that the more BDNF expression levels, the less feeding latency (anxiety-like behavior) and the less immobility (depressive-like behavior), meaning an indirect relationship (inverse relationship). By contrast, it showed that the more BDNF expression level, the more locomotor activity, the more pain threshold, and the more climbing, meaning a direct relationship. In conclusion, it can be suggested that CB1r activation in the CA1 region may interact with REM SD effects on behavioral functions and BDNF levels. For the first time, we showed that BDNF function in the CA1 region may modulate the effects of REM SD and CB1r activation on behavioral functions.

Keywords: ACPA; CB1 receptor; REM sleep deprivation; brain‐derived neurotrophic factor (BDNF); cannabinoid; mood.