The hippocampus and cortex of the mammalian brain are regions involved in learning and long-term memory. Estrogen and lithium affect similar learning and memory molecular processes. We hypothesized that in ovariectomized mice lithium treatment will enhance genetic factors in the brain that are involved in neuroprotection, learning and memory. Our study used bilaterally ovariectomized (bOVX) C57BL÷6J mice treated for one month with 14.2 mM LiCl in their drinking water. Results indicate that LiCl-treated bOVX mice show enhanced cortical increases in mRNA expression of ER-alpha, NR1, Bcl-2, BDNF, and CaMkII-alpha; hippocampal mRNA showed no changes. Our results indicate that in bOVX C57BL÷6J mice, lithium enhances the expression of specific cortical genes coded for proteins involved in learning, memory and neuroprotection.