Anandamide effects on 5-HT(3) receptors in vivo.

Studies in knockout mouse strains have shown that some cannabimimetic effects persist in animals lacking cannabinoid CB(1) and CB(2) receptors. These residual effects are thought to result, in part, from a cannabinoid-modulation of ion channels. This study investigates the role of 5-HT(3) receptors as a potential in vivo target for cannabinoids. Mice deficient in CB(1) and CB(2) receptors were treated with Delta(9)-tetrahydrocannabinol and anandamide, in the presence of the 5-HT(3) antagonist ondansetron. We show that the cannabinoid receptor-independent anandamide analgesia, but not catalepsy, is completely blocked by ondansetron. Thus, 5-HT(3) receptors seem to be involved in cannabinoid analgesia.