Two Peptides From the Endocannabinoid System Had Opposite Effects on Anxiety and Depression in Rats
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Hemopressin increased anxiety and depression; RVD-hemopressin produced the opposite effects
- Evidence Grade:
- Animal study with a single acute dose. Preliminary evidence revealing a novel mechanism with potential therapeutic significance.
- Study Age:
- Published in 2017.
- Original Title:
- Emotional disorders induced by Hemopressin and RVD-hemopressin(α) administration in rats.
- Published In:
- Pharmacological reports : PR, 69(6), 1247-1253 (2017)
- Authors:
- Leone, Sheila(2), Recinella, Lucia(2), Chiavaroli, Annalisa(2), Martinotti, Sara, Ferrante, Claudio, Mollica, Adriano, Macedonio, Giorgia, Stefanucci, Azzurra, Dvorácskó, Szabolcs, Tömböly, Csaba, De Petrocellis, Luciano, Vacca, Michele, Brunetti, Luigi, Orlando, Giustino
- Database ID:
- RTHC-01433
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is hemopressin?
Hemopressin is a naturally occurring peptide derived from hemoglobin that blocks CB1 cannabinoid receptors. In this study, it induced anxiety and depressive behavior while reducing mood-related brain chemicals in rats.
Could these peptides lead to new treatments for anxiety or depression?
Potentially. RVD-hemopressin showed anti-anxiety and antidepressant effects by positively influencing serotonin, dopamine, and norepinephrine levels, all of which are targets of current antidepressant medications. However, these are very early findings from a single animal study.
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Cite This Study
https://rethinkthc.com/research/RTHC-01433APA
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
MLA
Leone, Sheila, et al. "Emotional disorders induced by Hemopressin and RVD-hemopressin(α) administration in rats.." Pharmacological reports : PR, 2017. https://doi.org/10.1016/j.pharep.2017.06.010
RethinkTHC
RethinkTHC Research Database. "Emotional disorders induced by Hemopressin and RVD-hemopress..." RTHC-01433. Retrieved from https://rethinkthc.com/research/leone-2017-emotional-disorders-induced-by
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.