Changes in the Orexin System in Rats Exhibiting Learned Helplessness Behaviors

Orexin-A (OX-A) and orexin-B (OX-B) are neuropeptides produced in the hypothalamus. Preclinical and clinical studies suggest that depression and anxiety are associated with the orexin system. In the current study, we used the learned helplessness (LH) animal model of depression to identify rats displaying LH behaviors (LH rats) and those that did not (No-LH rats). We compared the number of orexin-containing neurons in the hypothalamus of LH, No-LH, and control rats. Orexin peptides, orexin receptor 1 (OXR1) and 2 (OXR2) in brain areas involved in major depression and serum OX-A and corticosterone (CORT) concentrations were quantified and compared between rat groups. We found that LH and No-LH rats displayed higher serum OX-A concentrations compared with control rats. Comparison between LH and No-LH rats revealed that No-LH rats had significantly higher OX-A levels in the brain, more OX-A neurons, and more OX-A neuron activation. LH rats had more OX-B neurons and more OX-B neuron activation. Orexin peptides and receptors in the brain areas involved in major depression exhibited different patterns in LH and NoLH rats. Our findings revealed that activation of OX-A neurons could promote resilient behaviors under stressful situations and OX-A and OX-B neuropeptides exhibit dissimilar functions in LH behaviors.