The modulatory role of the lateral septum on neuroendocrine and behavioral stress responses

Georg M Singewald (1) , Alesja Rjabokon (1) , Nicolas Singewald (1) , Karl Ebner (1)

1 Department of Pharmacology and Toxicology and Center for Molecular Biosciences Innsbruck (CMBI)

The lateral septum (LS) has been shown to play a key role in emotional processes and stress responses. However, the exact role of the LS upon stress modulation is not clear, since previous lesion studies mostly used electrolytic lesions, thereby destroying the whole septal area including medial components and/or fibres of passage. The aim of the present study was therefore, to investigate the effects of selective excitotoxic ablation of the LS on neuroendocrine and behavioral stress responses in rats. Bilateral ibotenic-acid lesions of the LS increased hypothalamo-pituitary-adrenocortical (HPA) axis responses to forced swim stress indicated by enhanced plasma ACTH and corticosterone responses and higher stress-induced c-Fos-like immunoreactivity in the paraventricular hypothalamic nucleus. Moreover, LS-lesioned animals displayed a more passive coping-style in the forced-swim-test indicated by increased floating and reduced struggling/swimming-behavior compared to sham-lesioned controls. Interestingly, intraseptal corticosteroid-receptor blockade modulated behavioral stress-coping but failed to change HPA-axis stress responses. Further experiments aimed at elucidating underlying neurochemical mechanisms revealed that intraseptal administration of the selective 5-HT1A receptor antagonist WAY-100635 increased and prolonged stress-induced ACTH and corticosterone levels mimicking lesion effects, while the agonist 8-OH-DPAT suppressed HPA-axis activity facilitating the inhibitory role of the LS. Additionally, 8-OH-DPAT injected animals showed increased active and decreased passive coping strategies during forced swimming suggesting antidepressant efficacy. Taken together, our data suggest that the LS promotes active stress coping behavior and is involved in a HPA-inhibitory mechanism that is at least in part mediated by septal 5-HT1A receptors and does not involve a glucocorticoid mediated feedback mechanism.

Mots clés: coping; glucocorticoids; Mood; Anxiety; Stress Disorders; Neurochemistry; Neuroendocrinology; Neuropharmacology; septum; HPA axis; stress

Georg M Singewald, Alesja Rjabokon, Nicolas Singewald, Karl Ebner. The modulatory role of the lateral septum on neuroendocrine and behavioral stress responses. Neuropsychopharmacology, 2010, ⟨10.1038/npp.2010.213⟩. ⟨hal-00600446⟩