Propofol pretreatment increases antidepressant-like effects induced by acute administration of ketamine in rats receiving forced swimming test

Animal and clinical studies have demonstrated that ketamine has quick, obvious and persistent antidepressant-like effect, but such side effects as cardiovascular system excitement and hallucinogenic activity have limited its clinical application. Intravenous anesthetic propofol can remarkably inhibit or eliminate ketamine's side effects including cardiovascular system excitement and hallucinogenic activity even in a sub-anesthesia dose. However, effect of propofol on rapid antidepressant-like action induced by ketamine still remains unclear. The present study aimed to investigate effect of pretreatment with propofol on the ketamine-induced rapid antidepressant-like action in rats receiving forced swimming test. Open field test and forced swimming test were used to investigate behavior changes of rats receiving different medication. Expression of brain derived neurotrophic factors (BDNF) and a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) pGluR1-Ser845 in hippocampus was measured with sandwich-ELISA and Western Blot, respectively. Results demonstrated that rats receiving propofol alone showed neither antidepressant-like effects nor increased BDNF content; pretreatment with propofol could increase the ketamine-induced antidepressant-like effects and the expression of AMPA pGluR1-Ser845 in hippocampus, but could not further reinforce the increased BDNF content induced by ketamine in hippocampus; after AMPA receptor was antagonized, the strengthening effect of propofol on ketamine-induced antidepressant-like action significantly decreased. The results indicated that propofol in a sub-anesthetic dose could increase the ketamine-induced antidepressant-like effect.