The potential efficacy of GABAB antagonists in depression

•The GABAB receptor has been linked to emotional behavior and depression.•Prior work indicates that a GABAB antagonist could be an effective antidepressant.•New selective, brain-penetrant GABAB antagonists are needed to test this hypothesis. Evidence for the potential utility of GABAB antagonists has been assembled from a variety of sources, including clinical experience with the GABAB agonist baclofen, murine genetic GABAB knock-outs, rodent studies of GABAB receptor expression and function following treatment with antidepressant therapies, animal models of depression, and some functional and post mortem data from human subjects. Definitive testing of GABAB antagonists in depression, however, still awaits the development of potent, selective and brain-penetrant compounds for human testing.