Prolactin-Releasing Peptide Contributes to Stress-Related Mood Disorders and Inhibits Sleep/Mood Regulatory Melanin-Concentrating Hormone Neurons in Rats

• DOI: 10.1523/jneurosci.2139-21.2022
• Publication Date: 2022-12-23T18:50:14Z
• Authors: Szilvia Vas; Rege S. Papp; Katalin Könczöl; Emese Bogáthy; Noémi Papp; Csaba Ádori; Máté Durst; Klaudia Sípos; Klementina Ocskay; Imre Farkas; Flóra Bálint; Szilamér Ferenci; Bibiána Török; Anita Kovács; Evelin Szabó; Dóra Zelena; Krisztina J. Kovács; Anna Földes; Erzsébet Kató; László Köles; György Bagdy; Miklós Palkovits; Zsuzsanna E. Tóth
• Keywords: Melanin-concentrating hormone; Sleep

Stress disorders impair sleep and quality of life; however, their pathomechanisms are unknown. Prolactin-releasing peptide (PrRP) is a stress mediator; we therefore hypothesized that PrRP may be involved in the development disorders. produced by medullary A1/A2 noradrenaline (NA) cells, which transmit signals to forebrain centers, non-NA cells hypothalamic dorsomedial nucleus. We found male rats both PrRP-NA innervate melanin-concentrating hormone (MCH) producing neurons dorsolateral hypothalamus (DLH). These serve as key hub for regulating affective states. Ex vivo , hyperpolarized MCH further increased hyperpolarization caused NA. Following deprivation, intracerebroventricular injection reduced number REM sleep-active cells. expression nucleus was upregulated while downregulated rebound. Both learned helplessness paradigm after peripheral inflammation, impaired coping with sustained associated (1) overactivation (2) protein receptor depletion DLH, (3) dysregulation expression. Exposure PrRP-insensitive period led passive stress. Normal signaling, therefore, seems protect animals against stress-related signaling DLH an important component PrRP's action, mediated neurons. Moreover, receptors were human suicidal victims. As mental leading cause suicide, our findings have particular translational relevance. SIGNIFICANCE STATEMENT Treatment resistance monoaminergic antidepressants major problem. Neuropeptides modulate central promising targets developing alternative therapeutic strategies. stress-responsive prolactin-releasing innervated crucial regulation mood. inhibited cell activity enhanced inhibitory effect evoked noradrenaline, classic monoamine, on observed failure chronic/repeated altered alterations system also subjects. dysfunction underlie disorders, fine-tuning part mechanism.