The role of the posterior medial bed nucleus of the stria terminalis in modulating hypothalamic–pituitary–adrenocortical axis responsiveness to acute and chronic stress

Abstract

SummaryThe bed nucleus of the stria terminalis (BST) plays a prominent role in brain integration of acute responses to stressful stimuli. This study tests the hypothesis that the BST plays a complementary role in regulation of physiological changes associated with chronic stress exposure. Male SpragueDawley rats received bilateral ibotenate lesions or sham lesions of the posterior medial region of the BST (BSTpm), an area known to be involved in inhibition of HPA axis responses to acute stress. Chronic stress was induced by 14-day exposure to twice daily stressors in an unpredictable sequence (chronic variable stress (CVS)). On the morning after the end of CVS, stressed and nonstressed controls were exposed to a novel restraint stress challenge. As previously documented, CVS caused adrenal hypertrophy, thymic involution, and attenuated body weight gain. None of these endpoints were affected by BSTpm lesions. Chronic stress exposure facilitated plasma corticosterone responses to the novel restraint stress and elevated CRH mRNA. Lesions of the BSTpm increased novel stressor-induced plasma ACTH and corticosterone secretion and enhanced c-fos mRNA induction in the paraventricular nucleus of the hypothalamus (PVN). In addition, lesion of the BSTpm resulted in an additive increase in CVS-induced facilitation of corticosterone responses and PVN CRH expression. Collectively these data confirm that the BSTpm inhibits HPA responses to acute stress, but do not strongly support an additional role for this region in limiting HPA axis responses to chronic drive. The data further suggest that acute vs. chronic stress integration are subserved by different brain circuitry.

Noradrenergic neurotransmission within the bed nucleus of the stria terminalis modulates the retention of immobility in the rat forced swimming test

“…Most notably, the influence of noradrenergic neurotransmission in the BNST on HPA activity should be considered (Cecchi et al, 2002a;Morilak et al, 2005). The BNST, through its different anatomical subnuclei, depending on the type and duration of stress exposure, plays a key role in HPA axis activity, inhibiting or stimulating it (Choi et al, 2007(Choi et al, , 2008. The stressinduced release of noradrenaline into the BNST seems to activate the neural circuits involved in HPA axis activation, with the participation of local a 1 adrenoceptors (Cecchi et al, 2002a(Cecchi et al, , 2002bPardon et al, 2003;Morilak et al, 2005).…”

“…In fact, the BNST is activated by different stressful stimuli (Greenwood et al, 2005;Beijamini and Guimaraes, 2006;Muigg et al, 2007) and plays an important role in the regulation of the activity of the hypothalamicpituitary-adrenal (HPA) axis in response to stress (Forray and Gysling, 2004;Choi et al, 2007Choi et al, , 2008. Moreover, exposure to inescapable stress elicits structural changes in the BNST (Pego et al, 2008), as well as in the amygdala (Roozendaal et al, 2009), hippocampus (Rodrigues et al, 2009), and medial prefrontal cortex (Izquierdo et al, 2006), often accompanied by increased anxiety-like and depressive-like behaviors in rodents (Cryan et al, 2002;Izquierdo et al, 2006;Rodrigues et al, 2009;De Paula Soares et al, 2011).…”

Social Status and Sex Effects on Neural Morphology in Damaraland Mole-Rats, <i>Fukomys damarensis</i>

“…The BSTp and MeA are involved in the processing of pheromonal input in other rodents and have associated roles in controlling neuroendocrine function and sexual behavior [Simerly, 2002]. The BSTp has also been implicated in the regulation of stress responses in other rodents via its projections to the PVN [Choi et al, 2008]. While the relationship between stress and social status in naked mole-rats is not simple Faulkes, 1997, 1998], it seems likely that at least some components of the hypothalamic-pituitaryadrenal axis are affected when an animal becomes a breeder.…”

Hypothalamic‐Pituitary‐Adrenal Axis—Feedback Control

“…The CRH neurons of the PVN receive inhibitory GABAergic projections from the bed nucleus of the stria terminalis (BNST) which relays information from the PFC (234) as well as the hippocampus (235). Studies using lesions of subnuclei of the BNST in rats demonstrate a posteriormedial region of the BNST acts as the relay from limbic structures to PVN (36,37). Lesions of the lateral fornix have shown that the ventral subiculum of the hippocampus projects to the PVN and results in increased CRH and AVP expression in the medial parvocellular PVN, and affect stress responsiveness of the HPA axis (23,46,116,233,235,253), suggesting a tonic suppression of PVN-releasing hormones by corticosteroid action in hippocampus.…”