Estrogen replacement therapy (ERT) is commonly prescribed during menopause. Post-menopausal women also tend to suffer from bipolar disorders and as a result are prescribed mood stabilizers – in addition to ERT. There is a paucity of data on how combined hormones and mood stabilizers interact in regulating gene expression that led us to hypothesize that in primary cultures of mixed brain cells predominated by glia, combined 17β-estradiol (E2) and lithium chloride (LiCl) (E2/LiCl) will alter estrogen receptor-alpha (ER-α) mRNA expression. We quantified mRNA expression of ER-α using the cDNA of treated primary cultures of mixed brain cells from a previous study. Our results indicate that hippocampal cultures predominated by glia increase in ER-α mRNA expression when treated for 48 h with combined E2/LiCl. Our findings may encourage further investigation on the molecular mechanisms involved in combined estrogen and lithium treatment