The effect of globopentaosylceramide on a depression model, mouse forced swimming

We investigated the late effects of serotonergic drugs on mouse forced swimming and found that serotonin 1A antagonist NAN-190 hydrobromide (NAN-190) and serotonin 2 agonist R(-)-DO1 hydrochloride (DO1) increase the typical anti-depressive behavior climbing 6 hours after the intraperitoneal injection. With the use of ion exchanger, ultra filtration and chemical extraction methods, a substance having remarkable anti-depressive activity on mouse forced swimming was extracted from the serums of the mice treated with the drugs. The substance was strongly suggested to be a glycolipid having a specific sugar chain structure GalNAcalpha1-3GalNAc in its terminal. In fact, globopentaosylceramide, another glycolipid having the structure in the terminal also showed marked anti-depressive activity on mouse forced swimming, but globotetraosylceramide lacking the sugar chain structure did not. The GalNAcalpha1-3GalNAc-lipid reactivity in the serum and typical anti-depressive behavior climbing increased corresponding to the doses of NAN-190 and DO1. These findings clearly indicate that the terminal structure GalNAcalpha1-3GalNAc has the essential role in the anti-depressive activity of globopentaosylceramide, and that serotonin 1A antagonism and serotonin 2 agonism increase the production of an anti-depressive glycolipid having the terminal structure in mouse serum.