Prolactin-Releasing Peptide System as a Potential Mechanism of Stress Coping: Studies in Male Rats

Int J Mol Sci. 2025 Apr 27;26(9):4155. doi: 10.3390/ijms26094155.

Abstract

Prolactin-releasing peptide (PrRP) has a regulatory role in both acute and chronic stress, suggesting its potential contribution to stress-related disorders such as depression. However, not all individuals with depression respond equally to stressors. We aimed to determine whether the PrRP system could underlie stress coping, an important aspect of depression. The forced swim test was used both as a stressor and as a method to assess coping strategy. Based on immobility time, active coping and passive coping subgroups were identified, and 10 brain regions were studied using qPCR to measure the mRNA expression levels of PrRP and its receptors (specific: GPR10; non-specific: NPFFR2). Passive coping animals spent more time in an immobile posture and exhibited altered mRNA expression levels in the medullary A1 region, the habenula, and the arcuate nucleus than control or active coping rats. Additionally, we identified corticotropin-releasing hormone and vesicular glutamate transporter 2 positive neurons in the A1 medullary region that contained Prrp, suggesting a modulatory role of PrRP in these excitatory neurons involved in stress regulation. Our findings reinforce the hypothesis that PrRP plays a role in stress coping, a process closely linked to depression. However its effect is brain region-specific.

Keywords: RNAscope; active coping; depression; forced swim test; mRNA expression; passive coping; prolactin-releasing peptide.

MeSH terms

  • Adaptation, Psychological*
  • Animals
  • Brain / metabolism
  • Depression / metabolism
  • Male
  • Neurons / metabolism
  • Prolactin-Releasing Hormone* / genetics
  • Prolactin-Releasing Hormone* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Psychological* / genetics
  • Stress, Psychological* / metabolism

Substances

  • Prolactin-Releasing Hormone