EXPLORING THE STRESS-DEPENDENT EFFECTS OF INTRANASAL MELANINCONCENTRATING HORMONE ADMINISTRATION ON ANXIETY-RELATED BEHAVIORS IN RATS

Abstract

Stress is a major risk factor for depression and anxiety, which are highly prevalent and frequently comorbid disorders. Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a key component of the stress response and is often dysregulated in these conditions. The hypothalamic neuropeptide Melanin-Concentrating Hormone (MCH) modulates emotional states and the stress response, although its role remains unclear. We previously showed that MCH administration intra-Locus Coeruleus aggravated helpless behavior in stressed rats using the learned helplessness paradigm. Additionally, acute intranasal (i.n.) MCH induced anhedonic-like behavior in the sucrose preference test in stressed animals. These findings suggest a functional interaction between MCH signalling and stress; however, the underlying mechanisms remain unclear. Here, we hypothesized that the pro-depressive effects of i.n. MCH in stressed animals are accompanied by increased anxiety-like behavior and activation of the HPA axis, as evidenced by increased corticotropin-releasing factor (CRF; a key component of the HPA axis) expression in the hypothalamic paraventricular nucleus. Adult male Wistar rats received acute i.n. MCH (15 µg) or vehicle. Behavior was assessed in the open field and light-dark box tests, in non-stressed and acutely stressed (15 min forced swim) animals. Results showed that neither stress exposure, MCH administration nor their interaction, produced significant effects under our experimental conditions. These results suggest that MCH-stress interactions may differentially regulate depression- and anxiety-like behaviors, supporting a behavior-specific role of MCH in emotional regulation. Ongoing experiments will determine CRF mRNA expression by RT-qPCR to further evaluate the involvement of MCH in HPA axis regulation.