Anandamide effects on 5-HT3 receptors in vivo

Studies in knockout mouse strains have shown that some cannabimimetic effects persist in animals lacking cannabinoid CB1 and CB2 receptors. These residual effects are thought to result, in part, from a cannabinoid-modulation of ion channels. This study investigates the role of 5-HT3 receptors as a potential in vivo target for cannabinoids. Mice deficient in CB1 and CB2 receptors were treated with Δ9-tetrahydrocannabinol and anandamide, in the presence of the 5-HT3 antagonist ondansetron. We show that the cannabinoid receptor-independent anandamide analgesia, but not catalepsy, is completely blocked by ondansetron. Thus, 5-HT3 receptors seem to be involved in cannabinoid analgesia.