Galphimia glauca and Natural Galphimines Block Schizophrenia-Like Symptoms Induced with Apomorphine and MK-801 in Mice

BACKGROUND: Galphimia glauca has been used for many years in Mexican Traditional Medicine to calm “insane people.” Triterpenes, known as galphimines, were identified in this species. One of them, Galphimine-B (G-B), acts selectively on dopaminergic neurons by antagonizing the effect of glutamate on NMDA receptors. The objective of this study was to evaluate the effect of G. glauca methanolic extract (GgMeOH), a Galphimine-Rich Fraction (GRF), as well as the galphimines G-A, G-B, and G-E, on the acute psychosis induced by Apomorphine (APO) in mice and on schizophrenia-like symptoms induced by subchronic administration of MK-801. METHOD: On the first day, ICR male mice were given GgMeOH, GRF, or one of the galphimines. On day two, animals were treated with APO, and on day 3, they were subjected to behavioral tests. In a second test, MK-801 was administered daily for 28 days. In this case, animals were treated daily with G. glauca products from day 9 to day 28 and then subjected to behavioral tests (passive avoidance test, open field test, forced swimming test, and social interaction test). RESULTS: The increased number of stereotyped behaviors and grooming behaviors induced with APO were counteracted by all of the experimental treatments. MK-801 induced an increase in immobility time, which was blocked with G-B; GRF counteracted the decreased social interaction, and GgMeOH and GRF prevented the memory loss induced by MK-801. CONCLUSION: G. glauca and their derivatives products (GRF and galphimines) were able to interact with the dopaminergic and glutamatergic drugs and to block different behaviors associated with some of the positive, negative, and cognitive symptoms of induced schizophrenia in mice. It is necessary to continue with this research, in order to identify their mechanism of action.