The Mesolimbic Dopamine Reward Circuit in Depression

Nestler, Eric J.; Carlezon, William A.

doi:10.1016/j.biopsych.2005.09.018

Cited by 1,800 publications

(1,389 citation statements)

References 103 publications

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“…By acting in the VTA, galanin could inhibit the mesolimbic dopaminergic system (Tsuda et al, 1998;Ericson and Ahlenius, 1999), which may affect (impair) both motor activity and reward mechanisms, related to depression (see Weiss et al, 1998Weiss et al, , 2005Nestler and Carlezon, 2006). In line with this hypothesis, infusion of galanin into the VTA significantly increased immobility time in the FST, while infusion of the galanin antagonist M15 had an antidepressant-like effect (Weiss et al, 1998(Weiss et al, , 2005.…”

Section: Integrative Mechanism Of Galanininergic Regulation Of Depresmentioning

confidence: 89%

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

Kuteeva

Wardi

Lundström

et al. 2008

Neuropsychopharmacol

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The present study on rat examined the role of galanin receptor subtypes in regulation of depression-like behavior as well as potential molecular mechanisms involved in the locus coeruleus (LC) and dorsal raphe (DR). The effect of intracerebroventricular (i.c.v.) infusion of galanin or galanin receptor GalR1-and GalR2-selective ligands was studied in the forced swim test, followed by quantitative in situ hybridization studies. Naive control, non-treated (swim control), saline-and fluoxetine-treated rats were used as controls in the behavioral and in situ hybridization studies. Subchronic treatment with fluoxetine reduced immobility and climbing time. Intracerebroventricular infusion of galanin, the GalR1 agonist M617 or the GalR2 antagonist M871 increased, while the GalR2(R3) agonist AR-M1896 decreased, immobility time compared to the aCSF-treated animals. Galanin also decreased the time of climbing. Galanin mRNA levels were upregulated by the combination of injection + swim stress in the saline-and the fluoxetine-treated groups in the LC, but not in the DR. Also tyrosine hydroxylase levels in the LC were increased following injection + swim stress in the saline-and fluoxetine-treated rats. Tryptophan hydroxylase 2 and serotonin transporter mRNAs were not significantly affected by any treatment. 5-HT 1A mRNA levels were downregulated following i.c.v. galanin, M617 or AR-M1896 infusion. These results indicate a differential role of galanin receptor subtypes in depression-like behavior in rodents: GalR1 subtype may mediate 'prodepressive' and GalR2 'antidepressant' effects of galanin. Galanin has a role in behavioral adaptation to stressful events involving changes of molecules important for noradrenaline and/or serotonin transmission.

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Section: Integrative Mechanism Of Galanininergic Regulation Of Depresmentioning

confidence: 89%

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

Kuteeva

Wardi

Lundström

et al. 2008

Neuropsychopharmacol

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“…Support for this higher sensitivity to a dysfunctional or stressful social environment in rs53576 G allele carriers was further substantiated by both observational (Burkhouse et al, 2015; Dannlowski et al, 2015; Hostinar et al, 2014; Smearman et al, 2015; Sturge-Apple et al, 2012; Windle and Mrug, 2015) and experimental studies (Chen et al, 2011; McQuaid et al, 2015; Norman et al, 2012). As examples of observational studies, it could be shown that rs53576 GG homozygous subjects with ELS exposure have a smaller bilateral volume of the ventral striatum, a key structure of the dopaminergic nigrostriatal pathway (Dannlowski et al, 2015) which is implicated in both depression risk (Nestler and Carlezon, 2006) and parenting behavior (Strathearn et al, 2009). Moreover, GG homozygous adolescents with ELS reported significantly lower social support as well as higher internalizing problems compared to A allele carriers (Hostinar et al, 2014).…”

Section: Gene-environment Interactions and Epigenetic Modificationmentioning

confidence: 99%

Oxytocin pathways in the intergenerational transmission of maternal early life stress

Toepfer

Heim

Entringer

et al. 2017

Neuroscience & Biobehavioral Reviews

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Severe stress in early life, such as childhood abuse and neglect, constitutes a major risk factor in the etiology of psychiatric disorders and somatic diseases. Importantly, these long-term effects may impact the next generation. The intergenerational transmission of maternal early life stress (ELS) may occur via pre-and postnatal pathways, such as alterations in maternal-fetal-placental stress physiology, maternal depression during pregnancy and postpartum, as well as impaired mother-offspring interactions. The neuropeptide oxytocin (OT) has gained considerable attention for its role in modulating all of these assumed transmission pathways. Moreover, central and peripheral OT signaling pathways are highly sensitive to environmental exposures and may be compromised by ELS with implications for these putative transmission mechanisms. Together, these data suggest that OT pathways play an important role in the intergenerational transmission of maternal ELS in humans. By integrating recent studies on gene-environment interactions and epigenetic modifications in OT pathway genes, the present review aims to develop a conceptual framework of intergenerational transmission of maternal ELS that emphasizes the role of OT.

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“…Alterations in 5-HT2C receptors have also been observed in suicide victims (Niswender et al, 2001). Deficits in dopaminergic signaling in the mesolimbic pathway have been implicated in the anhedonia associated with depression and psychostimulant drug withdrawal (Nestler and Carlezon, 2006). Many of the symptoms of depression resemble the negative symptoms of schizophrenia (e.g.…”

Section: Depression/anxietymentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

535

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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The Mesolimbic Dopamine Reward Circuit in Depression

Cited by 1,800 publications

References 103 publications

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

Oxytocin pathways in the intergenerational transmission of maternal early life stress

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

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