Hemopressin, a CB1 receptor antagonist peptide, induced anxiety and depressive behavior in rats, while RVD-hemopressin, a negative allosteric modulator, produced the opposite anti-anxiety and antidepressant effects.
Read this if you are interested in how natural peptides in the body regulate the endocannabinoid system and influence anxiety and mood.
Hemopressin increased anxiety and depression; RVD-hemopressin produced the opposite effects
What the researchers found
This study tested two naturally occurring peptides that modulate the endocannabinoid system and found they produce opposite emotional effects in rats.
Hemopressin, which blocks CB1 receptors (acting as an antagonist/inverse agonist), induced anxiogenic (anxiety-promoting) and depressive behavior when injected. At the neurochemical level, it decreased levels of norepinephrine, dopamine, and serotonin in the prefrontal cortex while increasing the enzymes that break these neurotransmitters down.
RVD-hemopressin, a longer peptide that acts as a negative allosteric modulator of CB1, produced the opposite effects: it reduced anxiety, decreased depressive behavior, increased monoamine levels, and decreased the breakdown enzymes in the prefrontal cortex.
Both peptides are derived from the hemoglobin alpha chain, and their opposing effects suggest that the endocannabinoid system has multiple peptide-based regulatory mechanisms with distinct behavioral consequences.
Why it matters
This study reveals that the endocannabinoid system has peptide regulators with direct effects on mood-related brain chemistry. The opposing effects of these two peptides provide new targets for understanding and potentially treating anxiety and depression through the endocannabinoid system.
The numbers in context
Both peptides dosed at 0.05 mg/kg intraperitoneally. Hemopressin decreased monoamines and increased MAO-B and COMT expression. RVD-hemopressin increased monoamines and decreased MAO-B and COMT expression in the prefrontal cortex.
How the study worked
Rats received single intraperitoneal injections of hemopressin (0.05 mg/kg) or RVD-hemopressin (0.05 mg/kg). Behavior was assessed using the locomotor activity/open field test, light-dark exploration test, and forced swim test. Prefrontal cortex levels of norepinephrine, dopamine, and serotonin were measured by HPLC. Gene expression of MAO-B and COMT (neurotransmitter-degrading enzymes) was measured by RT-PCR.
What this study cannot tell us
Single-dose, acute study in rats. The forced swim test and other behavioral measures are screening tools, not models of human depression. The peptides were injected peripherally, and their brain penetration and natural circulating levels are not well characterized.
How to read the evidence
Animal study with a single acute dose. Preliminary evidence revealing a novel mechanism with potential therapeutic significance.
When this study was published
Published in 2017.
The bigger picture
The finding that hemoglobin-derived peptides can modulate the endocannabinoid system and emotional behavior adds a new layer to our understanding of mood regulation. The opposing effects of these two related peptides mirror the complexity seen with other endocannabinoid compounds where different modulators of the same receptor system produce different behavioral outcomes.
Questions still open
- Are these peptides naturally circulating at levels that affect mood in humans? Could RVD-hemopressin or similar compounds be developed as antidepressant or anxiolytic medications? Do mood disorders involve altered levels of these endocannabinoid-modulating peptides?
Common questions
What is hemopressin?
Could these peptides lead to new treatments for anxiety or depression?
Read the original research
Emotional disorders induced by Hemopressin and RVD-hemopressin(α) administration in rats.
Pharmacological reports : PR, 69(6), 1247-1253
Citation
Leone, Sheila; Recinella, Lucia; Chiavaroli, Annalisa; Martinotti, Sara; Ferrante, Claudio; Mollica, Adriano; Macedonio, Giorgia; Stefanucci, Azzurra; Dvorácskó, Szabolcs; Tömböly, Csaba; De Petrocellis, Luciano; Vacca, Michele; Brunetti, Luigi; Orlando, Giustino. (2017). Emotional disorders induced by Hemopressin and RVD-hemopressin(α) administration in rats.. Pharmacological reports : PR, 69(6), 1247-1253. https://doi.org/10.1016/j.pharep.2017.06.010
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