The anti-nausea effects of CB1 agonists are mediated by an action at the visceral insular cortex

BACKGROUND AND PURPOSE

Conditioned gaping reactions reflect nausea-induced behaviour in rats. Cannabinoid 1 receptor (CB₁) agonists interfere with the establishment of nausea-induced conditioned gaping; however, it is not known if their effects are mediated by an action at peripheral or central CB₁ receptors.

EXPERIMENTAL APPROACH

We utilized the conditioned gaping model of nausea to evaluate the effect of peripheral and central administration of the peripherally restricted CB₁ agonist, CB13, on the establishment of LiCl-induced gaping in rats. We further evaluated the ability of HU-210 administered to the gustatory insular cortex (GIC) or visceral insular cortex (VIC) to interfere with LiCl-induced conditioned gaping and determined if this effect was mediated by CB₁ receptors.

KEY RESULTS

Central, but not peripheral, CB13 suppressed LiCl-induced conditioned gaping. Central administration of the potent CB₁ agonist, HU-210, delivered to the VIC, but not the GIC, suppressed the establishment of LiCl-induced gaping reactions, but not LiCl-induced suppression of hedonic reactions or conditioned taste avoidance. This pattern of results suggests that HU-210 delivered to the VIC prevented LiCl-induced nausea, but not learning per se. The suppression of LiCl-induced conditioned gaping by HU-210 was mediated by CB₁ receptors because it was prevented by co-administration of CB₁ antagonist/inverse agonist, AM-251, into the VIC. A high dose of AM-251 (20 µg) administered alone into the VIC did not produce conditioned gaping reactions.

CONCLUSIONS AND IMPLICATIONS

The nausea-relieving effects of CB₁ agonists, but not the nausea-inducing effects of CB₁ inverse agonists, are mediated, at least in part, by their action at the VIC in rats.