Effects of acute and chronic administration of antidepressant drugs on the central cholinergic nervous system

1983 ◽  
Vol 22 (10) ◽  
pp. 1215-1222 ◽  
Author(s):  
M.E. Goldman ◽  
C.K. Erickson
Keyword(s):  
Nervous System ◽  
Antidepressant Drugs ◽  
Chronic Administration

scholarly journals Exendin-4 increases blood glucose levels acutely in rats by activation of the sympathetic nervous system

2010 ◽  
Vol 298 (5) ◽  
pp. E1088-E1096 ◽  
Author(s):  
Diego Pérez-Tilve ◽  
Lucas González-Matías ◽  
Benedikt A. Aulinger ◽  
Mayte Alvarez-Crespo ◽  
Manuel Gil-Lozano ◽  
...  
Keyword(s):  
Nervous System ◽  
Blood Glucose ◽  
Sympathetic Nervous System ◽  
Mammalian Species ◽  
Chronic Administration ◽  
Acute Administration ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sympathetic Nervous ◽  
High Doses

Exendin-4 (Ex-4), an agonist of the glucagon-like peptide-1 receptor (GLP-1R), shares many of the actions of GLP-1 on pancreatic islets, the central nervous system (CNS), and the gastrointestinal tract that mediates glucose homeostasis and food intake. Because Ex-4 has a much longer plasma half-life than GLP-1, it is an effective drug for reducing blood glucose levels in patients with type 2 diabetes mellitus (T2DM). Here, we report that acute administration of Ex-4, in relatively high doses, into either the peripheral circulation or the CNS, paradoxically increased blood glucose levels in rats. This effect was independent of the insulinotropic and hypothalamic-pituitary-adrenal activating actions of Ex-4 and could be blocked by a GLP-1R antagonist. Comparable doses of GLP-1 did not induce hyperglycemia, even when protected from rapid metabolism by a dipeptidyl peptidase IV inhibitor. Acute hyperglycemia induced by Ex-4 was blocked by hexamethonium, guanethidine, and adrenal medullectomy, indicating that this effect was mediated by sympathetic nervous system (SNS) activation. The potency of Ex-4 to elevate blood glucose waned with chronic administration such that after 6 days the familiar actions of Ex-4 to improve glucose tolerance were evident. These findings indicate that, in rats, high doses of Ex-4 activate a SNS response that can overcome the expected benefits of this peptide on glucose metabolism and actually raise blood glucose. These results have important implications for the design and interpretation of studies using Ex-4 in rats. Moreover, since there are many similarities in the response of the GLP-1R system across mammalian species, it is important to consider whether there is acute activation of the SNS by Ex-4 in humans.

scholarly journals BIOCHEMICAL STUDIES OF HIPPOCAMPAL GENE EXPRESSION OF BRAIN-DERIVED NEUROTROPIC FACTOR AND TOLL-LIKE RECEPTOR-4 IN DIABETIC RATS EXPOSED TO CHRONIC STRESS: EFFECTS OF ANTIDEPRESSANT DRUGS

2018 ◽  
Vol 11 (1) ◽  
pp. 271
Author(s):  
Sawsan Aboul-fotouh ◽  
Doaa Mohamed Hassan ◽  
Mohamed Zaki Eldeen Habib ◽  
Ahmed Ibrahim Amin ◽  
Samar K. Kassim ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Antidepressant Drugs ◽  
Chronic Administration ◽  
Diabetic Rats ◽  
Toll Like Receptor ◽  
Bdnf Expression ◽  
Toll Like Receptor 4 ◽  
Inflammatory State ◽  
Neurotropic Factor ◽  
Factor Α

  Objective: Depression and diabetes are closely associated in a reciprocal manner, leading to significant morbidity and mortality with an evidence of a pro-inflammatory state underlying pathophysiology of both diseases. Unfortunately, little information is available about the effects of antidepressant drugs on hippocampal brain-derived neurotrophic factor (BDNF) and toll-like receptor-4 (TLR-4) expression in diabetes.Methods: We investigated the effect of chronic administration of fluoxetine (FLU) and imipramine (IMIP) on behavioral, metabolic, and inflammatory abnormalities in diabetic and non-diabetic rats exposed to chronic restraint stress (CRS).Results: Both diabetes and CRS induced depressive-like behavior which was more prominent in diabetic/depressed rats; this was reversed by chronic treatment with FLU and IMIP. Diabetic and non-diabetic rats exposed to CRS showed a significant increase in hippocampal expression of TLR-4 and pro-inflammatory cytokines alongside a decrease in BDNF expression. FLU and IMIP ameliorated these inflammatory abnormalities.Conclusion: Diabetes mellitus (DM) and chronic stress induced a depressive-like behavior associated with an increase in hippocampal expression of TLR-4, tumor necrosis factor-α, and interleukin-1ß with a significant correlation to decreased BDNF expression. FLU and IMIP showed comparable effects regards the improvement of depressive and inflammatory abnormalities associated with DM.

scholarly journals Systemic administration of a β2-adrenergic receptor agonist reduces mechanical allodynia and suppresses the immune response to surgery in a rat model of persistent post-incisional hypersensitivity

2021 ◽  
Vol 17 ◽  
pp. 174480692199720
Author(s):  
Vipin Arora ◽  
Carlos Eduardo Morado-Urbina ◽  
Young S Gwak ◽  
Renee A Parker ◽  
Carol A Kittel ◽  
...  
Keyword(s):  
Nervous System ◽  
Rat Model ◽  
Adrenergic Receptor ◽  
Chronic Administration ◽  
Mechanical Hypersensitivity ◽  
Beneficial Effects ◽  
Curve Modeling ◽  
Β2 Adrenergic Receptor ◽  
Plantar Incision ◽  
Anti Inflammatory

Beta 2 adrenergic receptor (β2 AR) activation in the central and peripheral nervous system has been implicated in nociceptive processing in acute and chronic pain settings with anti-inflammatory and anti-allodynic effects of β2-AR mimetics reported in several pain states. In the current study, we examined the therapeutic efficacy of the β2-AR agonist clenbuterol in a rat model of persistent postsurgical hypersensitivity induced by disruption of descending noradrenergic signaling in rats with plantar incision. We used growth curve modeling of ipsilateral mechanical paw withdrawal thresholds following incision to examine effects of treatment on postoperative trajectories. Depletion of spinal noradrenergic neurons delayed recovery of hypersensitivity following incision evident as a flattened slope compared to non-depleted rats (-1.8 g/day with 95% CI -2.4 to -1.085, p < 0.0001). Chronic administration of clenbuterol reduced mechanical hypersensitivity evident as a greater initial intercept in noradrenergic depleted (6.2 g with 95% CI 1.6 to 10.8, p = 0.013) and non-depleted rats (5.4 g with 95% CI 1.2 to 9.6, p = 0.018) with plantar incision compared to vehicle treated rats. Despite a persistent reduction in mechanical hypersensitivity, clenbuterol did not alter the slope of recovery when modeled over several days (p = 0.053) or five weeks in depleted rats (p = 0.64). Systemic clenbuterol suppressed the enhanced microglial activation in depleted rats and reduced the density of macrophage at the site of incision. Direct spinal infusion of clenbuterol failed to reduce mechanical hypersensitivity in depleted rats with incision suggesting that beneficial effects of β2-AR stimulation in this model are largely peripherally mediated. Lastly, we examined β2-AR distribution in the spinal cord and skin using in-situ hybridization and IHC. These data add to our understanding of the role of β2-ARs in the nervous system on hypersensitivity after surgical incision and extend previously observed anti-inflammatory actions of β2-AR agonists to models of surgical injury.

Impairment of trophic response of brown fat to cold in guanethidine-treated rats

1982 ◽  
Vol 242 (3) ◽  
pp. C159-C165 ◽  
Author(s):  
G. Mory ◽  
D. Ricquier ◽  
M. Nechad ◽  
P. Hemon
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Protein A ◽  
Chronic Administration ◽  
Phospholipid Content ◽  
Noradrenaline Content ◽  
Brown Adipose ◽  
Sympathetic Nervous ◽  
Binding To Mitochondria

The aim of the present study was to investigate the role of the sympathetic nervous system in the trophic response of brown adipose tissue (BAT) to chronic cold exposure. The hyperplasia and the development of the mitochondria characterizing this response are usually considered as mainly controlled by the sympathetic activity in BAT, but this has never been clearly demonstrated. In the present work rats were sympathectomized by chronic administration of guanethidine and then exposed to cold during two weeks. The treatment induced a strong reduction of the noradrenaline content of BAT. The trophic response of the tissue to cold was largely impaired: no increase of the tissue weight, weak increase in the DNA, protein, and phospholipid content of the tissue. The development of the mitochondria was almost abolished. The increase in the proportion of the 32,000-dalton protein, a protein which regulates heat production by BAT, was suppressed and the GDP-binding to mitochondria, which is an index of BAT thermogenic capacity, was not increased as in normal cold-adapted rats. The ultrastructure of the tissue remained the same as in warm-adapted animals. It is concluded that the sympathetic nervous system plays an essential role in the control of the trophic response of BAT to the cold.

scholarly journals The Relationship Between the Gut Microbiome-Immune System-Brain Axis and Major Depressive Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Jane A. Foster ◽  
Glen B. Baker ◽  
Serdar M. Dursun
Keyword(s):  
Nervous System ◽  
Major Depressive Disorder ◽  
Immune System ◽  
Depressive Disorder ◽  
Gut Microbiome ◽  
Antidepressant Drugs ◽  
Short Chain Fatty Acids ◽  
Major Depressive ◽  
Signaling Systems ◽  
Full Remission

Major depressive disorder (MDD) is a prominent cause of disability worldwide. Current antidepressant drugs produce full remission in only about one-third of MDD patients and there are no biomarkers to guide physicians in selecting the best treatment for individuals. There is an urgency to learn more about the etiology of MDD and to identify new targets that will lead to improved therapy and hopefully aid in predicting and preventing MDD. There has been extensive interest in the roles of the immune system and the gut microbiome in MDD and in how these systems interact. Gut microbes can contribute to the nature of immune responses, and a chronic inflammatory state may lead to increased responsiveness to stress and to development of MDD. The gut microbiome-immune system-brain axis is bidirectional, is sensitive to stress and is important in development of stress-related disorders such as MDD. Communication between the gut and brain involves the enteric nervous system (ENS), the autonomic nervous system (ANS), neuroendocrine signaling systems and the immune system, and all of these can interact with the gut microbiota. Preclinical studies and preliminary clinical investigations have reported improved mood with administration of probiotics and prebiotics, but large, carefully controlled clinical trials are now necessary to evaluate their effectiveness in treating MDD. The roles that several gut microbe-derived molecules such as neurotransmitters, short chain fatty acids and tryptophan play in MDD are reviewed briefly. Challenges and potential future directions associated with studying this important axis as it relates to MDD are discussed.

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