Blunted HPA Axis Response to Stress Influences Susceptibility to Posttraumatic Stress Response in Rats

The aim of this article is to summarize current evidence regarding alterations in the neuroendocrine stress response system and endocannabinoid system and their relationship in psychotic disorders such as schizophrenia. Exposure to stress is linked to the development of a number of psychiatric disorders including psychosis. However, the precise role of stress in the development of psychosis and the possible mechanisms that might underlie this are not well understood. Recently the cannabinoid hypothesis of schizophrenia has emerged as a potential line of enquiry. Endocannabinoid levels are increased in patients with psychosis compared with healthy volunteers; furthermore, they increase in response to stress, which suggests another potential mechanism for how stress might be a causal factor in the development of psychosis. However, research regarding the links between stress and the endocannabinoid system is in its infancy. Evidence summarized here points to an alteration in the baseline tone and reactivity of the hypothalamic–pituitary–adrenal (HPA) axis as well as in various components of the endocannabinoid system in patients with psychosis. Moreover, the precise nature of the inter-relationship between these two systems is unclear in man, especially their biological relevance in the context of psychosis. Future studies need to simultaneously investigate HPA axis and endocannabinoid alterations both at baseline and following experimental perturbation in healthy individuals and those with psychosis to understand how they interact with each other in health and disease and obtain mechanistic insight as to their relevance to the pathophysiology of schizophrenia.

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Chronic stress, hippocampus and parvalbumin-positive interneurons: what do we know so far?

Reviews in the Neurosciences ◽

10.1515/revneuro-2015-0042 ◽

2016 ◽

Vol 27 (4) ◽

pp. 397-409 ◽

Cited By ~ 17

Author(s):

Ivan Zaletel ◽

Dragana Filipović ◽

Nela Puškaš

Keyword(s):

Stress Response ◽

Mood Disorders ◽

Chronic Stress ◽

Hpa Axis ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Emotional Information ◽

Contextual Memory ◽

Response To Stress ◽

Unexplored Area

AbstractThe hippocampus is a brain structure involved in the regulation of hypothalamic-pituitary-adrenal (HPA) axis and stress response. It plays an important role in the formation of declarative, spatial and contextual memory, as well as in the processing of emotional information. As a part of the limbic system, it is a very susceptible structure towards the effects of various stressors. The molecular mechanisms of structural and functional alternations that occur in the hippocampus under chronic stress imply an increased level of circulating glucocorticoids (GCs), which is an HPA axis response to stress. Certain data show that changes induced by chronic stress may be independent from the GCs levels, opening the possibility of existence of other poorly explored mechanisms and pathways through which stressors act. The hippocampal GABAergic parvalbumin-positive (PV+) interneurons represent an especially vulnerable population of neurons in chronic stress, which may be of key importance in the development of mood disorders. However, cellular and molecular hippocampal changes that arise as a consequence of chronic stress still represent a large and unexplored area. This review discusses the current knowledge about the PV+ interneurons of the hippocampus and the influence of chronic stress on this intriguing population of neurons.

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Effects of L-3,4-dihydroxyphenylalanine (L-Dopa) Treatment in the Neuroendocrine Response to Stress

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.136 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A67-A68

Author(s):

Santiago Jordi Orrillo ◽

Mercedes Imsen ◽

Alfonsina Lizarraga ◽

Ana Clara Romero ◽

Fernanda De Fino ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Stress Response ◽

Hpa Axis ◽

Sympathetic Nerves ◽

Serum Levels ◽

Male Wistar Rats ◽

Response To Stress ◽

Behavioural Tests ◽

Hpa Axis Activity

Abstract Stressful stimuli evoke a complex response mediated by two systems: the Sympathetic-Adreno-Medullar (SAM) axis and the Hypothalamus-Pituitary-Adrenal (HPA) axis. Among the factors involved in stress, glucocorticoids and catecholamines secreted from the adrenal glands and sympathetic nerves are the main effectors of the physiological adaptations to stressors. Besides these, prolactin (PRL) is another hormone secreted under stress conditions. Catecholamines are synthesized from the hydroxylated precursor L-Dopa. This agent is commonly used for the treatment of Parkinson’s disease and it would act as a neurotransmitter per se. On the other hand, it has been suggested that HPA axis dysregulation is a potential risk factor for the development of depression. In line with this, several studies reported that L-Dopa treatment may alter the serum levels of ACTH, PRL, and glucocorticoids in parkinsonian patients and Parkinson’s disease animal models. In the present study, we determined whether the chronic treatment with L-Dopa altered the stress response inducing depressive-like behaviours. Adult male Wistar rats were treated orally during 24 days with LEBOCAR® - commercial formulation of L-Dopa (75 mg/day) and Carbidopa (7.5 mg/day) - in drinking water. Animals were stressed by immobilization during the last 9 days of treatment and depressive-like behaviours were assessed by the sucrose intake and forced swimming tests. Behavioural tests showed no signs of depressive-like behaviours in the LEBOCAR®-treated and/or stressed rats. We next explored the SAM axis reactivity. Circulating noradrenaline and adrenaline increased in rats treated with LEBOCAR® (p<0.05; HPLC). Also, the adrenals from stressed animals showed higher content of adrenaline (p<0.05). Then, we studied the HPA axis activity. Chronically stressed rats displayed a lower ACTH secretion (ELISA) and a downregulation of POMC expression (qPCR) in the anterior pituitary (p<0.05). In addition, LEBOCAR® treatment induced a reduction in serum ACTH and POMC levels (p<0.05). As expected, serum corticosterone (ELISA) enhanced under chronic stress, an effect that was inhibited by treatment with LEBOCAR® (p<0.05). Finally, pituitary PRL gene expression (qPCR) was downregulated by LEBOCAR® treatment with a more pronounced effect when rats were also stressed (p<0.05). Our results suggest that L-Dopa alters the neuroendocrine stress response enhancing SAM axis reactivity and reducing HPA axis activity and PRL expression.

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