Emotional disorders induced by Hemopressin and RVD-hemopressin(α) administration in rats

Pharmacol Rep. 2017 Dec;69(6):1247-1253. doi: 10.1016/j.pharep.2017.06.010. Epub 2017 Jun 23.

Abstract

Background: The endocannabinoid (eCB) system plays an important role in regulating emotional disorders, and is involved, directly or indirectly, in psychiatric diseases, such as anxiety and depression. Hemopressin, a hemoglobin α chain-derived peptide, and RVD-hemopressin(α), a N-terminally extended form of hemopressin, act as antagonist/inverse agonist and negative allosteric modulator of the cannabinoid 1 (CB1) receptor, respectively.

Methods: Considering the possible involvement of these peptides on emotional behaviour, the aim of our study was to investigate the behavioural effects of a single intraperitoneal (ip) injection of hemopressin (0.05mg/kg) and RVD-hemopressin(α) (0.05mg/kg), using a series of validated behavioural tests (locomotor activity/open field test, light-dark exploration test, forced swim test) in rats. Prefrontal cortex levels of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) and the gene expression of monoamine oxidase (MAO-B) and catechol-O-methyltransferase (COMT) were measured by high performance liquid chromatography (HPLC) analysis and real-time reverse transcription polymerase chain reaction (RT-PCR), respectively.

Results: Hemopressin administration induced anxiogenic and depressive behaviour, decreased monoamine steady state levels in prefrontal cortex, and increased the gene expression of the enzymes involved in their catabolism. By contrast, RVD- hemopressin(α) induced anxiolytic and antidepressive effects, increased monoamines and decreased the enzymes in prefrontal cortex.

Conclusion: In conclusion, in the present study we demonstrated behavioral effects induced by peripheral hemopressin and RVD-hemopressin(α) injections, that could involve modulatory effects on monoaminergic signaling, in the prefrontal cortex.

Keywords: Anxiety; Depression; Hemopressin; Monoamines; RVD-hemopressin(α).

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety / physiopathology
  • Behavior, Animal / drug effects*
  • Catechol O-Methyltransferase / metabolism
  • Chromatography, High Pressure Liquid
  • Depression / chemically induced
  • Depression / physiopathology
  • Dopamine / metabolism
  • Hemoglobins / administration & dosage
  • Hemoglobins / pharmacology*
  • Injections, Intraperitoneal
  • Male
  • Norepinephrine / metabolism
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / metabolism

Substances

  • Hemoglobins
  • Peptide Fragments
  • RVD-hemopressin, human
  • hemopressin
  • Serotonin
  • Catechol O-Methyltransferase
  • Dopamine
  • Norepinephrine