GABA(B) receptors within the lateral habenula modulate stress resilience and vulnerability in mice

Resilience means "the ability to withstand or recover quickly in the face of adversity". Elucidating the neural and molecular mechanisms underlying stress resilience will facilitate the development of more effective treatments for stress-induced psychiatric disorders such as depression. The habenular nuclei, which consist of the medial and lateral sub-regions (MHb and LHb, respectively), have been described as a critical node in emotional regulations. GABA(B) receptors play an important regulatory role in habenular activity. In this study, we assessed the functional role of GABA(B) receptors within the habenula in stress resilience and vulnerability by using chronic social defeat stress (CSDS) model in C57BL/6 male mice. Approximately 47.1% of mice exhibited depression- or anxiety-like behaviors after exposure to CSDS. The vulnerable mice presented elevated c-Fos expression in the LHb when confronted with an attacker. On the other hand, the expression of GABA(B) receptors, including both GABA(B1) and GABA(B2) subunits, was significantly down-regulated in the LHb of the susceptible mice. Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by intra-LHb injection of both baclofen and CGP36216 (a GABA(B) receptor agonist and antagonist respectively). The above results indicated that GABA(B) receptors in the LHb may play an important role in stress resilience and vulnerability, and thus, may be an important therapeutic target for treatments of stress-induced psychiatric disorders.