Infusion of galanin into the mid-caudal portion of the dorsal raphe nucleus has an anxiolytic effect on rats in the elevated T-maze

Silote, Gabriela Pandini; Rosal, Aline Boroto; Souza, Mayara Machado de; Beijamini, Vanessa

doi:10.1016/j.bbr.2013.06.023

Cited by 10 publications

(4 citation statements)

References 48 publications

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“…These findings are consistent with a study in goldfish, showing icv injection of OX to stimulate locomotor activity [71, 73, 74], and also with studies in rodents, showing central administration of OX to stimulate locomotor activity and arousal [75, 76] while GAL has no effect on these behaviors [77]. The finding here, that injection of neither GAL nor OX affect exploratory activity indicating no change in anxiety, contrasts with results in rats showing GAL to cause a reduction in anxiety [77, 78] while OX stimulates it [79]. Thus, the evidence described here suggests that GAL and OX have distinct functions in zebrafish, with GAL acting more specifically to stimulate ethanol intake and OX stimulating locomotor activity while acting more generally to increase consummatory behavior.…”

Section: Discussionsupporting

confidence: 56%

Effects of embryonic ethanol exposure at low doses on neuronal development, voluntary ethanol consumption and related behaviors in larval and adult zebrafish: Role of hypothalamic orexigenic peptides

Sterling

Chang

Karatayev

et al. 2016

Behavioural Brain Research

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Embryonic exposure to ethanol is known to affect neurochemical systems in rodents and increase alcohol drinking and related behaviors in humans and rodents. With zebrafish emerging as a powerful tool for uncovering neural mechanisms of numerous diseases and exhibiting similarities to rodents, the present report building on our rat studies examined in zebrafish the effects of embryonic ethanol exposure on hypothalamic neurogenesis, expression of orexigenic neuropeptides, and voluntary ethanol consumption and locomotor behaviors in larval and adult zebrafish, and also effects of central neuropeptide injections on these behaviors affected by ethanol. At 24 h post-fertilization, zebrafish embryos were exposed for 2 h to ethanol, at low concentrations of 0.25% and 0.5%, in the tank water. Embryonic ethanol compared to control dose-dependently increased hypothalamic neurogenesis and the proliferation and expression of the orexigenic peptides, galanin (GAL) and orexin (OX), in the anterior hypothalamus. These changes in hypothalamic peptide neurons were accompanied by an increase in voluntary consumption of 10% ethanol-gelatin and in novelty-induced locomotor and exploratory behavior in adult zebrafish and locomotor activity in larvae. After intracerebroventricular injection, these peptides compared to vehicle had specific effects on these behaviors altered by ethanol, with GAL stimulating consumption of 10% ethanol-gelatin more than plain gelatin food and OX stimulating novelty-induced locomotor behavior while increasing intake of food and ethanol equally. These results, similar to those obtained in rats, suggest that the ethanol-induced increase in genesis and expression of these hypothalamic peptide neurons contribute to the behavioral changes induced by embryonic exposure to ethanol.

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Section: Discussionsupporting

confidence: 56%

Effects of embryonic ethanol exposure at low doses on neuronal development, voluntary ethanol consumption and related behaviors in larval and adult zebrafish: Role of hypothalamic orexigenic peptides

Sterling

Chang

Karatayev

et al. 2016

Behavioural Brain Research

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“…With this study focusing on the measures of exploration in a novel environment, which is an indicator of anxiety, and aggressive behavior, there is some evidence in the fish literature pointing to the possibility that orexigenic peptides mediate the effects of ethanol on behavior. While little is known about the relationship of these peptides to aggressive behavior and of GAL to ethanol intake, intracerebroventricular injection of OX in goldfish does stimulate locomotor activity [61, 64], a behavior closely associated with the overconsumption of ethanol in the rodent [11, 35], and studies in rats have linked endogenous GAL expression to increased locomotor activity in a novel environment [11] and show central injection of GAL to reduce anxiety [66, 67]. Collectively, our findings demonstrate for the first time a direct relationship between ethanol and the orexigenic peptides in zebrafish, demonstrating that voluntary ingestion of ethanol dramatically changes peptide expression.…”

Section: Discussionmentioning

confidence: 99%

Model of voluntary ethanol intake in zebrafish: Effect on behavior and hypothalamic orexigenic peptides

Sterling

Karatayev

Chang

et al. 2015

Behavioural Brain Research

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Recent studies in zebrafish have shown that exposure to ethanol in tank water affects various behaviors, including locomotion, anxiety and aggression, and produces changes in brain neurotransmitters, such as serotonin and dopamine. Building on these investigations, the present study had two goals: first, to develop a method for inducing voluntary ethanol intake in individual zebrafish, which can be used as a model in future studies to examine how this behavior is affected by various manipulations, and second, to characterize the effects of this ethanol intake on different behaviors and the expression of hypothalamic orexigenic peptides, galanin (GAL) and orexin (OX), which are known in rodents to stimulate consumption of ethanol and alter behaviors associated with alcohol abuse. Thus, we first developed a new model of voluntary intake of ethanol in fish by presenting this ethanol mixed with gelatin, which they readily consume. Using this model, we found that individual zebrafish can be trained in a short period of time to consume stable levels of 10% or 20% ethanol (v/v) mixed with gelatin and that their intake of this ethanol-gelatin mixture leads to pharmacologically-relevant blood ethanol concentrations which are strongly, positively correlated with the amount ingested. Intake of this ethanol-gelatin mixture increased locomotion, reduced anxiety, and stimulated aggressive behavior, while increasing expression of GAL and OX in specific hypothalamic areas. These findings, confirming results in rats, provide a method in zebrafish for investigating with forward genetics and pharmacological techniques the role of different brain mechanisms in controlling ethanol intake.

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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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Infusion of galanin into the mid-caudal portion of the dorsal raphe nucleus has an anxiolytic effect on rats in the elevated T-maze

Cited by 10 publications

References 48 publications

Effects of embryonic ethanol exposure at low doses on neuronal development, voluntary ethanol consumption and related behaviors in larval and adult zebrafish: Role of hypothalamic orexigenic peptides

Effects of embryonic ethanol exposure at low doses on neuronal development, voluntary ethanol consumption and related behaviors in larval and adult zebrafish: Role of hypothalamic orexigenic peptides

Model of voluntary ethanol intake in zebrafish: Effect on behavior and hypothalamic orexigenic peptides

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

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