Co-treatment with cannabidiol and escitalopram in ineffective doses induces antidepressant effect in maternally separated male adolescent rats.

Due to low efficacy and delayed therapeutic effect of drugs currently used in the therapy of depression in adolescent population, a lot of effort has been put into finding new substances using alternative target points that could support treatment with traditional antidepressive drugs. Cannabidiol, compound derived from Cannabis sativa may have therapeutic potential in depressive disorders. This study aimed to investigate whether combined administration of escitalopram with cannabidiol in ineffective doses, will provide better or similar effects in behavioral tests compared to escitalopram in an effective dose in adolescent maternally separated rats. Maternal separation has been used as a form of early life adversity. The pups were separated from their dams for 360 min daily from postnatal day (PND) 2 until PND 15. Later, escitalopram (15 or 5 mg/kg) or vehicle were administered ip. in a subacute manner in mid-adolescent male rats. Cannabidiol (15 mg/kg) or vehicle were injected ip. in a single dose about 1 h prior to behavioral assessment. Three standard behavioral tests were performed: the elevated plus maze and the open field test on PND 42 and the forced swimming test on PND 43-44 on the subsequent groups of rats. The combined treatment with escitalopram and cannabidiol in ineffective doses did not induce anxiolytic-like effects but successfully relieved despair behavior in the forced swimming test showing similar efficacy as treatment with escitalopram in effective dose. This result might be the basis for future research and the development of new therapeutic strategies for treatment of adolescent depression.