A compound meant to mimic the effects of natural cannabinoids was found to reverse the short and long-term deficits caused by repeated social defeat in a new study published by the journal Neuropsychopharmacology.
Psychosocial stress contributes to the development of psychiatric disorders. Repeated social defeat (RSD) is a murine stressor that causes a release of inflammatory monocytes into circulation. Moreover, RSD-induced anxiety-like behavior is dependent on the recruitment of these monocytes to the brain.
With this in mind, it’s important to note that “Activation of the endocannabinoid (ECB) system [done naturally through the consumtion of cannabinoids] may modulate both neuroendocrine and inflammatory responses mediated by stress”, states the study’s researchers. “Therefore, we hypothesized that a cannabinoid receptor agonist would attenuate RSD-induced inflammation, anxiety, and stress sensitization.”
To test this hypothesis, “mice received an injection of the synthetic cannabinoid1/2 receptor agonist, WIN55,212-2 (WIN; 1 mg/kg, intraperitoneally) daily for six consecutive days, 30 min before each exposure to RSD. Anxiety-like behavior, immune activation, neuroinflammation, and microglial reactivity were determined 14 h[ours] after RSD.”
RSD-induced anxiety-like behavior ” was reversed by WIN55,212-2″. Moreover, “WIN55,212-2 reduced the accumulation of inflammatory monocytes in circulation and brain after RSD and attenuated RSD-induced interleukin-1β (IL-1β) messenger RNA (mRNA) expression in microglia/macrophages. Increased ex vivo reactivity of microglia/monocytes to lipopolysaccharides (LPS) after RSD was also attenuated by WIN55,212-2.”
Next, “fear expression, extinction, and recall were evaluated 24 and 48 h, respectively, after contextual fear conditioning, which took place 7 days after RSD. Here, RSD caused prolonged fear expression and impaired fear extinction recall, which was associated with increased IL-1β mRNA in the brain.” Moreover, “these stress-induced effects were reversed by WIN55,212-2.”
The study concludes by stating that “activation of cannabinoid receptors limited the immune and neuroinflammatory responses to RSD and reversed the short-term and long-term behavioral deficits associated with RSD.”