Substance P receptor antagonist in lateral habenula improves rat depression-like behavior

Substance P (SP) levels are closely related with the pathogenesis of depression. Recent work has focused on antidepressive effect of substance Preceptor antagonist (SPA), however, its action site and mechanism remain largely unresolved. Our previous results showed that the lateral habenula (LHb) plays a key role in the pathogenesis of depression. The current study investigated the effects of SPA microinjected into LHb on the behavioral responses of two rat models that exhibit depression-like behavior. To produce adult rats that exhibit depression-like behavior, rats were either exposed to chronic mild stress (CMS), or chronically administered clomipramine (CLI), a tricyclic antidepressant, during the neonatal state of life. The forced-swimming test (FST) was used to evaluate behavioral responses. Furthermore, we measured serotonin (5-HT) levels in dorsal raphe nucleus (DRN) using microdialysis. The FST showed a decreased immobility time and an increased climbing time after SPA injection into the LHb of depression-like behavior rats. In addition, 5-HT levels in DRN increased after SPA was microinjected into LHb of the rats that exhibited depression-like behavior. This study demonstrates that LHb mediates antidepressive effect of SPA by increasing 5-HT levels in the DRN, suggesting that the LHb may be a potential target of antidepressant. (C) 2013 Elsevier Inc. All rights reserved.