Kami-ondam-tang, a traditional herbal prescription, attenuates the prepulse inhibition deficits and cognitive impairments induced by MK-801 in mice

Abstract

Ethnopharmacological relevanceKami-ondam-tang (KODT) has been used to treat neuropsychiatric disorders, including neurosis and insomnia, in traditional herbal medicine. However, the mechanisms of this drug have not been well characterized in the treatment of schizophrenia-like behaviors. Aim of the studyWe investigated whether schizophrenia-like behaviors induced by MK-801, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, could be attenuated by KODT. Materials and methodsAcute systemic administration of MK-801 was used to establish an animal model of schizophrenia. The effects of KODT on the MK-801-induced prepulse inhibition (PPI) deficits, hyperlocomotion, social withdrawal, and cognitive impairment were assessed. We also examined the changes in the expression levels of Akt and extracellular signal-regulated kinase (ERK) after the administration of KODT with MK-801 in the cortical and hippocampal tissues. ResultsThe acoustic startle response test showed that the acoustic startle enhancement and PPI deficits induced by MK-801 were attenuated by KODT. Moreover, KODT ameliorated social and objective recognition impairments that were induced by MK-801 in the social novelty preference test and the novel object recognition test. In addition, the upregulation of phosphorylated Akt or phosphorylated ERK expression induced by MK-801 was blocked by KODT in the cortex. However, MK-801-induced hyperlocomotion was not affected by KODT in the open field test. ConclusionThese findings suggest that KODT attenuates MK-801-induced PPI disruption, social interaction deficits, and cognitive impairments, possibly, by regulating of cortical Akt and ERK signaling.