Escitalopram reverses anxiety-like and despair behavior and affects endocannabinoid-related genes expression in the brain of adolescent male rats subjected to early life stress

Due to the increasing prevalence of depressive and anxiety disorders in youth, a growing interest in the endocannabinoid system (ECS) as a potential alternative target point for treatment arised. This study aimed to investigate whether chronic administration of escitalopram reverses behavioral changes induced by maternal separation in male adolescent Wistar rats and explore the corresponding neurochemical changes in the ECS. The pups were separated from their dams for 360 min daily from postnatal day (PND) 2 until PND 15. Later, male rats were administered escitalopram (10 mg/kg i.p.) during their adolescent period (PND 35 - PND 55). Behavioral assessments were conducted in late adolescence (PND 54 - PND 57) in one group, and brain structures were dissected for biochemical analysis in the subsequent group of rats on PND 56. Expression of genes encoding: CB1 receptor, enzyme that catalyzes synthesis (NAPE-PLD) and degradation (FAAH) of anandamide (a full agonist of CB1 receptor) was evaluated using qRT-PCR. The corresponding protein levels were estimated via Western blot analysis. Our study revealed that maternal separation induced anxiety and despair-like behavior in adolescent rats. Escitalopram reversed anxiety-like behavior and attenuated signs of despair behavior. The escitalopram administration has been followed by a decrease in the studied genes expression in the amygdala, the hypothalamus, and the hippocampus, what might suggest that the endocannabinoid system is involved in the mechanism of its action in adolescents. However Western blot analysis did not indicate significant alterations in the protein levels, so more detailed studies are needed to verify this hypothesis.