The antidepressant-like effect of galanin in the dorsal raphe nucleus of rats involves GAL 2 receptors

Souza, Mayara Machado de; Silote, Gabriela Pandini; L, Herbst; Funck, Vinícius Rafael; Joca, Sâmia Regiane Lourenço; Beijamini, Vanessa

doi:10.1016/j.neulet.2018.05.029

Cited by 16 publications

(7 citation statements)

References 41 publications

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“…This provides further evidence that galanin is released in vivo under stressful conditions. More recently it has been shown that an anxiolytic-/antidepressive effect of galanin injected directly into the DRN is mediated via GalR2 (Silote et al, 2013; de Souza et al, 2018).…”

Section: Galanin and Depression-like Behavior In Rodentsmentioning

confidence: 99%

Neuropeptide and Small Transmitter Coexistence: Fundamental Studies and Relevance to Mental Illness

Hökfelt

Barde

et al. 2018

Front. Neural Circuits

100

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Neuropeptides are auxiliary messenger molecules that always co-exist in nerve cells with one or more small molecule (classic) neurotransmitters. Neuropeptides act both as transmitters and trophic factors, and play a role particularly when the nervous system is challenged, as by injury, pain or stress. Here neuropeptides and coexistence in mammals are reviewed, but with special focus on the 29/30 amino acid galanin and its three receptors GalR1, -R2 and -R3. In particular, galanin’s role as a co-transmitter in both rodent and human noradrenergic locus coeruleus (LC) neurons is addressed. Extensive experimental animal data strongly suggest a role for the galanin system in depression–like behavior. The translational potential of these results was tested by studying the galanin system in postmortem human brains, first in normal brains, and then in a comparison of five regions of brains obtained from depressed people who committed suicide, and from matched controls. The distribution of galanin and the four galanin system transcripts in the normal human brain was determined, and selective and parallel changes in levels of transcripts and DNA methylation for galanin and its three receptors were assessed in depressed patients who committed suicide: upregulation of transcripts, e.g., for galanin and GalR3 in LC, paralleled by a decrease in DNA methylation, suggesting involvement of epigenetic mechanisms. It is hypothesized that, when exposed to severe stress, the noradrenergic LC neurons fire in bursts and release galanin from their soma/dendrites. Galanin then acts on somato-dendritic, inhibitory galanin autoreceptors, opening potassium channels and inhibiting firing. The purpose of these autoreceptors is to act as a ‘brake’ to prevent overexcitation, a brake that is also part of resilience to stress that protects against depression. Depression then arises when the inhibition is too strong and long lasting – a maladaption, allostatic load, leading to depletion of NA levels in the forebrain. It is suggested that disinhibition by a galanin antagonist may have antidepressant activity by restoring forebrain NA levels. A role of galanin in depression is also supported by a recent candidate gene study, showing that variants in genes for galanin and its three receptors confer increased risk of depression and anxiety in people who experienced childhood adversity or recent negative life events. In summary, galanin, a neuropeptide coexisting in LC neurons, may participate in the mechanism underlying resilience against a serious and common disorder, MDD. Existing and further results may lead to an increased understanding of how this illness develops, which in turn could provide a basis for its treatment.

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Section: Galanin and Depression-like Behavior In Rodentsmentioning

confidence: 99%

Neuropeptide and Small Transmitter Coexistence: Fundamental Studies and Relevance to Mental Illness

Hökfelt

Barde

et al. 2018

Front. Neural Circuits

100

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“…81 Of course, previous studies showed that some antidepressants block 5-HT2A receptors while others elicit antidepressant action via activation of 5-HT1AR. 85 In line with the aforementioned explanations, various ligands, models and their effects, including the action of synthetic peptide, J18 17 are presented in Table 1.…”

Section: Galanin In Depressionmentioning

confidence: 90%

<p>Galanin Receptors as Drug Target for Novel Antidepressants: Review</p>

Demsie

Altaye

Weldekidan

et al. 2020

BTT

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Galanin (GAL) is a 29-amino-acid neuropeptide that serves multiple physiological functions throughout the central and peripheral nervous system. Its role involves in a range of physiological and pathological functions including control of food intake, neuroprotection, neuronal regeneration, energy expenditure, reproduction, water balance, mood, nociception and various neuroendocrine functions. The use of currently available antidepressant drugs raises concerns regarding efficacy and onset of action; therefore, the need for antidepressants with novel mechanisms is increasing. Presently, various studies revealed the link between GAL and depression. Attenuation of depressive symptoms is achieved through inhibition of GalR1 and GalR3 and activation of GalR2. However, lack of receptor selectivity of ligands has limited the complete elucidation of effects of different receptors in depression-like behavior. Studies have suggested that GAL enhances the action of selective serotonin reuptake inhibitors (SSRIs) and promotes availability of transcription proteins. This review addresses the role of GAL, GAL receptors (GALRs) ligands including selective peptides, and the mechanism of ligand receptor interaction in attenuating depressive symptoms.

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“…However, administration of the 5-HT1AR agonist 8-OH-DPAT, or SSRI fluoxetine [189] in combination with GAL(1-15), reduced depressive-like behaviors, and this effect was blocked by inhibition of the 5HT1AR [190]. The GALR2 antagonist, M871, increased depressive behaviors and increased anxiety-like behaviors in rats [191] while the administration of the GAL2 agonist AR-M1896 [192] or an active galanin analog [193] produced antidepressant effects. Altogether, this indicates that targeting GALR1-GALR2-5-HT1AR heteroreceptor complexes might be a promising future therapeutic strategy to treat depression.…”

Section: Galanin Receptorsmentioning

confidence: 99%

Novel Pharmacological Approaches to the Treatment of Depression

Elias

Zhang

Manners

2022

Life

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Major depressive disorder is one of the most prevalent mental health disorders. Monoamine-based antidepressants were the first drugs developed to treat major depressive disorder. More recently, ketamine and other analogues were introduced as fast-acting antidepressants. Unfortunately, currently available therapeutics are inadequate; lack of efficacy, adverse effects, and risks leave patients with limited treatment options. Efforts are now focused on understanding the etiology of depression and identifying novel targets for pharmacological treatment. In this review, we discuss promising novel pharmacological targets for the treatment of major depressive disorder. Targeting receptors including N-methyl-D-aspartate receptors, peroxisome proliferator-activated receptors, G-protein-coupled receptor 39, metabotropic glutamate receptors, galanin and opioid receptors has potential antidepressant effects. Compounds targeting biological processes: inflammation, the hypothalamic-pituitary-adrenal axis, the cholesterol biosynthesis pathway, and gut microbiota have also shown therapeutic potential. Additionally, natural products including plants, herbs, and fatty acids improved depressive symptoms and behaviors. In this review, a brief history of clinically available antidepressants will be provided, with a primary focus on novel pharmaceutical approaches with promising antidepressant effects in preclinical and clinical studies.

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The antidepressant-like effect of galanin in the dorsal raphe nucleus of rats involves GAL 2 receptors

Cited by 16 publications

References 41 publications

Neuropeptide and Small Transmitter Coexistence: Fundamental Studies and Relevance to Mental Illness

Neuropeptide and Small Transmitter Coexistence: Fundamental Studies and Relevance to Mental Illness

<p>Galanin Receptors as Drug Target for Novel Antidepressants: Review</p>

Novel Pharmacological Approaches to the Treatment of Depression

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