GABA_B receptors, depression, and stress resilience

In the central nervous system, gamma-aminobutyric acid (GABA) acts on two types of receptors: ionotropic GABAA and GABAC receptors and metabotropic GABAB receptors. Functional GABAB receptors are heterodimers of GABAB1 and GABAB2 subunits, and in the brain the GABAB1 subunit is expressed as two main isoforms, GABAB1a and GABAB1b. In this chapter, we summarize the evidence of a role for the GABAB receptor in depression and the response to stress and antidepressant drugs. We then review the relatively new findings that the GABAB1a and GABAB1b subunit isoforms differentially regulate stress resilience. Finally, we discuss the neurobiological processes that potentially underpin the differential roles of these subunits in modulating stress resilience, including the serotonin neurotransmitter system, the hypothalamic-pituitary-adrenal axis, and adult hippocampal neurogenesis.