Activation of serotonin2C receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat

Han, Ling-Na; Zhang, Li; Li, Libo; Sun, Yajuan; Wang, Yong; Chen, Li; Guo, Yuan; Zhang, Yuming; Zhang, Qiao-Jun; Liu, Jian

doi:10.1016/j.neuropharm.2015.01.024

Cited by 58 publications

(38 citation statements)

References 77 publications

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“…These findings were replicated using other procedures. Similar consequences of LHb lesion were reported in a 6-OHDA rat model of parkinson’s disease (31), while on the contrary, LHb activation using a 5-HT2C agonist decreased monoamine levels and increased depressive-like behaviors in hemiparkinsonian rats (32). Pharmacological inhibition of LHb by the GABA agonist muscimol had antidepressant effects in congenital helpless rats (33), and opposite metabolic alterations in Hb (high) and VTA (low) were observed in these rats (34).…”

Section: Depressionsupporting

confidence: 59%

Translating the Habenula—From Rodents to Humans

Boulos

Darcq

Kieffer

2017

Biological Psychiatry

142

125

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The habenula (Hb) is a central structure connecting forebrain to midbrain regions. This microstructure regulates monoaminergic systems, notably dopamine and serotonin, and integrates cognitive with emotional and sensory processing. Early preclinical data have described Hb as a brain nucleus activated in anticipation of aversive outcomes. Evidence has now accumulated to show that Hb encodes both rewarding and aversive aspects of external stimuli, thus driving motivated behaviors and decision-making. Human Hb research is still nascent but develops rapidly, alongside with the growth of neuroimaging and deep brain stimulation techniques. Not surprisingly Hb dysfunction has been associated with psychiatric disorders, and studies in human patients have established evidence for Hb involvement in major depression, addiction and schizophrenia, as well as in pain and analgesia. Here we summarize current knowledge from animal research, and overview the existing human literature on anatomy and function of the Hb. We also discuss challenges and future directions in targeting this small brain structure in both rodents and humans. By combining animal data and human experimental studies, this review addresses the translational potential of preclinical Hb research.

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Section: Depressionsupporting

confidence: 59%

Translating the Habenula—From Rodents to Humans

Boulos

Darcq

Kieffer

2017

Biological Psychiatry

142

125

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“…The rapid antidepressant effects of ketamine, for example, are dependent on mTOR signaling in the medial PFC [40]. Exercise can reduce the incidence of depression [91] and can be used on its own [92–95] or as an adjunct to typical antidepressants [96, 97] for the treatment of depression. Similarly, both voluntary and forced wheel running result in an antidepressant-like effect in the shuttle box escape task [22].…”

Section: Discussionmentioning

confidence: 99%

Exercise increases mTOR signaling in brain regions involved in cognition and emotional behavior

Lloyd

Hake

Ishiwata

et al. 2017

Behavioural Brain Research

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Exercise can enhance learning and memory and produce resistance against stress-related psychiatric disorders such as depression and anxiety. In rats, these beneficial effects of exercise occur regardless of exercise controllability: both voluntary and forced wheel running produce stress-protective effects. The mechanisms underlying these beneficial effects of exercise remain unknown. The mammalian target of rapamycin (mTOR) is a translation regulator important for cell growth, proliferation, and survival. mTOR has been implicated in enhancing learning and memory as well as antidepressant effects. Moreover, mTOR is sensitive to exercise signals such as metabolic factors. The effects of exercise on mTOR signaling, however, remain unknown. The goal of the present study was to test the hypothesis that exercise, regardless of controllability, increases levels of phosphorylated mTOR (p-mTOR) in brain regions important for learning and emotional behavior. Rats were exposed to 6 weeks of either sedentary (locked wheel), voluntary, or forced wheel running conditions. At 6 weeks, rats were sacrificed during peak running and levels of p-mTOR were measured using immunohistochemistry. Overall, both voluntary and forced exercise increased p-mTOR-positive neurons in the medial prefrontal cortex, striatum, hippocampus, hypothalamus, and amygdala compared to locked wheel controls. Exercise, regardless of controllability, also increased numbers of p-mTOR-positive glia in the striatum, hippocampus, and amygdala. For both neurons and glia, the largest increase in p-mTOR positive cells was observed after voluntary running, with forced exercise causing a more modest increase. Interestingly, voluntary exercise preferentially increased p-mTOR in astrocytes (GFAP+), while forced running increased p-mTOR in microglia (CD11+) in the inferior dentate gyrus. Results suggest that mTOR signaling is sensitive to exercise, but subtle differences exist depending on exercise controllability. Increases in mTOR signaling could contribute to the beneficial effects of exercise on cognitive function and mental health.

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“…The effects of 5-HT on LHb neurons is complex and may have roles in addiction and depression (Meye et al, 2013). 5-HT activation of 5-HT2/3 receptors results in excitation of LHb neurons (Xie et al, 2016) and 5-HT7 as well as 5-HT2C receptors are involved in regulating depression-like behaviors in PD models (Han et al, 2015; 2016). …”

Section: Afferent Connectionsmentioning

confidence: 99%

Review of the cytology and connections of the lateral habenula, an avatar of adaptive behaving

Zahm

Root

2017

Pharmacology Biochemistry and Behavior

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The cytology and connections of the lateral habenula (LHb) are reviewed. The habenula is first introduced, after which the cytology of the LHb is discussed mainly with reference to cell types, general topography and descriptions of subnuclei. An overview of LHb afferent connections is given followed by some details about the projections to LHb from a number of structures. An overview of lateral habenula efferent connections is given followed by some details about the projections from LHb to a number of structures. In considering the afferent and efferent connections of the LHb some attention is given to the relative validity of regarding it as a bi-partite structure featuring ‘limbic’ and ‘pallidal’ parts. The paper ends with some concluding remarks about the relative place of the LHb in adaptive behaving.

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Activation of serotonin2C receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat

Cited by 58 publications

References 77 publications

Translating the Habenula—From Rodents to Humans

Translating the Habenula—From Rodents to Humans

Exercise increases mTOR signaling in brain regions involved in cognition and emotional behavior

Review of the cytology and connections of the lateral habenula, an avatar of adaptive behaving

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