GABAergic functions and depression: from classical therapies to herbal medicine

Classical medications employed to treat depression comprise mostly tricyclic antidepressants (TCAs), specific serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs), in accord with the recognized involvement of serotonergic and adrenergic systems in depression. Other therapies such as electro-convulsive shock, lithium intake and psychotherapy work via as yet unknown mechanisms. Although GABAergic neurotransmitter systems have not been central to etiological hypotheses for depression, observations are accumulating to suggest that these systems might play an important role in the induction of the disease. Lines of evidence in this regard include interactions between GABAergic and other neurotransmitter systems in depression, GABA levels in patients before and after antidepressant treatments, GABA levels and up/down regulations of GABA receptors in animal models of induced depression, and clinical effects of GABA receptor ligands. Phytomedicines that have a long history of useful applications are drawing increasing attention in pharmaceutical research. Moreover, while drug development is usually focused on single constituent drugs on account of their more accurately predictable physiological responses, complex herbal formulae represent an increasingly important source of drug discovery given the advent of high-throughput screening and specific receptor binding assays. Their active constituents acting on different neurotransmitter systems could be identified, and their therapeutic efficacies tested rigorously. Along with new insights into the underlying mechanisms of depression, the rich abundance of chemical entities from herbs is becoming an inviting resource in the search for effective treatment. This review addresses recent research on the possible role of GABAergic receptors with regard to depression, and potentially antidepressant phytomedicines acting on this class of receptors.