Another gene putatively, although not consistently, linked to bipolar disorder is the glycogen synthase kinase-3 (GSK-3). Although GSK-3 acts at multiple levels to regulate over 40 proteins, it is generally accepted that it acts as a proapoptotic agent. While increased apoptosis is consistent with the cellular loss that has been reported in bipolar disorder patients, the main interest in this target derives from the reports suggesting that antimanic treatment effects are mediated by GSK-3. Heterozygous GSK-3-mutant mice have been created and display increased activity levels and other behavioral abnormalities. The behavior of GSK-3 heterozygous mice resemble that of lithium-treated mice, however; thus, this model may be more applicable as a drug screen for lithium-like compounds. Moreover, there appears to be greater evidence linking GSK-3 inhibition with antidepressant- like activity than with mania-reducing effects. Hence, the suitability of the GSK-3 mutant mice as a model of bipolar disorder mania has been questioned.