Key result
Inhibition of AT1 receptors specifically within the subfornical organ blunted the release of ACTH and corticosterone in response to restraint stress and increased time spent in the open arms of an elevated-plus maze.
Why the study?
Does AT1R knockdown in the subfornical organ reduce stress-induced HPA activation and anxiety-like behavior in rats?
Does AT1R knockdown in the subfornical organ reduce stress-induced HPA activation and anxiety-like behavior in rats?
p-value: p=<0.05
Circulating angiotensin II acts on AT1 receptors in the subfornical organ to mediate hypothalamic-pituitary-adrenal axis activation and anxiety-like behavior in response to psychological stress.
Hypothesis-generating for central AT1R as stress target; requires human validation before any therapeutic consideration.
This study elucidates the neural circuits by which circulating angiotensin II (ANGII) acts in the brain to influence humoral and behavioral responses to psychological stressors. To test the hypothesis that systemic ANGII mediates stress responding via the subfornical organ (SFO), we first found that the timing of increased systemic ANGII in response to 60 min restraint coincides with increased c-fos mRNA expression in the SFO. Next, we administered an anterograde neuronal tract tracer into the SFO and found that fibers originating there make appositions onto neurons in the paraventricular nucleus of the hypothalamus that are also c-fos positive following restraint stress. To determine whether circulating ANGII stimulates the release of stress hormones via activation of angiotensin type 1 receptors (AT1R) within the SFO, we delivered lentivirus to knockdown AT1R expression locally in the SFO. Inhibition of AT1R specifically within the SFO blunted the release of adrenocorticotrophin-releasing hormone and corticosterone in response to restraint stress and caused rats to spend more time in the open arms of an elevated-plus maze than controls, indicating that inhibition of AT1R within the SFO is anxiolytic. Collectively, these results suggest that circulating ANGII acts on AT1R in the SFO to influence responding to psychological stressors.
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Krause et al. (2011) studied Psychogenic stress. Lentiviral knockdown of AT1R in the SFO (LV-AS) or systemic losartan vs. LV-GFP or saline vehicle was evaluated on ACTH and corticosterone release during restraint stress, and time spent in open arms of elevated-plus maze (p=<0.05). Inhibition of AT1 receptors specifically within the subfornical organ blunted the release of ACTH and corticosterone in response to restraint stress and increased time spent in the open arms of an elevated-plus maze.
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