Effect of Chronic in‐vivo Exposure to Opioid versus Cannabinoid Receptor Agonists on CB1 and mu‐Opioid Receptor Protein Level in the Guinea Pig Longitudinal Muscle‐Myenteric Plexus Model

Abstract

Similarities in opioid (OP) and cannabinoid (CB) signaling and their effects suggest that tolerance development may utilize similar signaling pathways. Previous studies using the longitudinal muscle‐myenteric plexus (LM/MP) showed selective reduction in potency and efficacy only to cannabinoid1 receptor (CB1) agonists after chronic CB exposure and reduced potency with no effect on efficacy for either OP or CB agonists after chronic OP treatment. The current study investigated the effect of chronic opioid and CB treatment on mu‐opioid (MOR) and CB1 receptor protein level in the LM/MP. We also explored the distribution and potential co‐localization of the receptors in LM/MP neurons. Tolerance was induced by chronic OP or CB receptor agonist injection. Receptor protein levels were assessed using Western blotting and receptor localization by immunofluorescence. Chronic CB treatment significantly reduced (32%) CB1 protein whereas MOR protein levels remained unchanged. Chronic OP treatment altered neither MOR nor CB1 protein levels. Significant co‐localization of CB1 and MOR was observed in the LM/MP with comparable density of immunopositive neurons for each receptor population. The current data reinforce the notion that tolerance observed with chronic CB treatment in this model involves receptor dependent changes, whereas tolerance to OP may involve non‐receptor dependent changes in cell excitability.