CB1 receptors on a subset of vagal afferent neurons modulate voluntary ethanol intake in mice

Herrerias, Alexa and Oliverio, Anna and Dvorácskó, Szabolcs and Thyagarajan, Arthi and Chedester, Lee and Liu, Jie and Cinar, Resat and Iyer, Malliga R. and Kunos, George and Godlewski, Grzegorz (2025) CB1 receptors on a subset of vagal afferent neurons modulate voluntary ethanol intake in mice. MOLECULAR PSYCHIATRY. ISSN 1359-4184

Preview

Text s41380-025-03266-9.pdf - Published Version Available under License Creative Commons Attribution. Download (5MB) | Preview

Abstract

Gut-brain signaling influences alcohol consumption and addiction behaviors. We found that selectively deleting cannabinoid receptor 1 (CB 1 R) from advillin + peripheral sensory neurons eliminates the inhibitory effect of the peripheral CB 1 R antagonist JD5037 on voluntary ethanol intake (VEI). Similar results were seen in mice with CB 1 R deletion in Phox2b + nodose ganglia (NGA), but not in Wnt + dorsal root ganglia. These findings were corroborated with MRI-1891, another non-brain penetrant CB 1 R antagonist. The inhibition of VEI by JD5037 was lost in Gpr65 Cre ; Cnr1 lox/lox mice but remained intact in Glp1r Cre ; Cnr1 lox/lox mice. Additionally, deleting the ghrelin receptor (Ghsr) from Phox2b + NGA neurons blocked the inhibition of alcohol intake either by a Ghsr or by CB 1 R antagonists. Thus, CB 1 R on Gpr65 + NGA projections to the mucosa of the gastrointestinal tract is essential for VEI. These findings also suggest a mutual interdependence of endocannabinoid and ghrelin signaling in controlling VEI via a gut-brain axis.

Actions (login required)

Edit Item