Maternal separation induces changes in TREK-1 and 5HT1A expression in brain areas involved in the stress response in a sex-dependent way

[Display omitted] •Postnatal stress induces behavioural despair in female, but not male juvenile rats.•MS increases TREK-1 in basolateral amygdala and prelimbic cortex.•5HT1A reduction in dentate gyrus is associated to behavioural despair in females.•TREK-1 increase in dentate gyrus is associated to behavioural despair in females.•More 5HT1A expression in basolateral amygdala is linked to resilience in males. Depression is a prevalent disease in modern society, and has been linked to stressful events at early ages. Women are more susceptible to depression, and the neural basis for this are still under investigation. Serotonin is known to be involved in depression, and a decrease in 5HT1A expression is observed on temporal and cortical areas in both men and women with depression. As knockout animals for TREK-1 are resilient to depression, this channel has emerged as a new potential pharmacological target for depression treatment. In this study, maternal separation (MS) was used to emulate early-life stress, and evaluate behaviour, as well as TREK-1 and 5HT1A expression in the brain using immunohistochemistry. In juvenile females, 5HT1A reduction coupled to increased TREK-1 in the dentate gyrus (DG) was associated with behavioural despair, as well as increased TREK-1 expression in basolateral amygdala (BLA) and prelimbic cortex (PL). In juvenile males, MS induced an increase in 5HT1A in the BLA, and in TREK-1 in the PL, while no behavioural despair was observed. Anhedonia and anxiety-like behaviour were not induced by MS. We conclude stress-induced increase in TREK-1 in PL and GD is associated to depression, while 5HT1A changes coupled to TREK-1 changes may be necessary to induce depression, with females being more vulnerable to MS effects than males. Thus, TREK-1 and 5HT1A may be potential pharmacological targets for antidepressants development.