In conclusion, this study draws attention to the role of combination therapy with memantine and aripiprazole in the alleviation of prenatal VPA-induced autistic-like and cognitive deficits which could be mediated via blocking NMDA receptor-mediated excitotoxicity and enhancing CREB/BDNF signaling with increased expression of astrocytic Glt-1 and subsequent restoration of GABA/glutamate balance and rescue of hippocampal neuronal survival. The gene discussed is CREB1; the disease is Cognitive impairment.