Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat

Näslund, Jakob; Studer, Erik; Nilsson, Karin; Westberg, Lars; Eriksson, Elias

doi:10.1007/s00213-013-3133-6

Cited by 25 publications

(21 citation statements)

References 60 publications

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“…This method almost completely eliminated Tph2 and 5-HT immunoreactivity in the dorsal raphe nucleus. Importantly, AADC, norepinephrine, and dopamine levels were unaffected, at least at 2 weeks after injection.The disruption of the 5-HT machinery selectively in serotonergic neurons not only confirmed previous findings regarding its role in sleep-wake cycles and locomotor activity (Alenina et al, 2009), but also revealed novel physiological and behavioral consequences. Although classical measures of anxiety-like behavior (i.e., time spent in bright/unprotected vs dark/ protected areas) were not affected by 5-HT depletion, a marked increase in locomotor activity in the open field was found.…”

supporting

confidence: 84%

“…Indeed, patients carrying a polymorphism of the Tph2 gene show higher susceptibility to develop ADHD (Sheehan et al, 2005). Accordingly, mice lacking the 5-HT transporter show higher 5-HT extracellular levels (Kim et al, 2005) and lower locomotor activity than controls (Kalueff et al, 2007). The hyperactive phenotype described by Whitney et al…”

Section: Fl/ϫmentioning

confidence: 99%

“…Moreover, dense serotonergic projections from the dorsal raphe reach the amygdala, where 5-HT modulates the activity of GABAergic interneurons (Woodruff and Sah, 2007), suggesting that 5-HT neurons modulate amygdala activity. It has been shown that glutamate and 5-HT corelease by dorsal raphe neurons signal reward (Liu et al, 2014). Investigating whether a similar mechanism is involved in the modulation of amygdala activity by 5-HT neurons would help explain the unaltered anxiety-like behavior of adult 5-HT-depleted mice.…”

Section: Fl/ϫmentioning

confidence: 99%

“…First, it would be interesting to test whether circuit level alterations take place following 5-HT depletion, which may account for the observed phenotype. Neurophysiological changes within the nucleus accumbens have been shown in Clock-⌬19 mice (Dzirasa et al, 2010), which may account for their hyperactive phenotype. The same group reported abnormal functional interactions in the mPFC-amygdala circuit in a mouse model of 5-HT deficiency with depressivelike behavior (Dzirasa et al, 2013).…”

Section: Fl/ϫmentioning

confidence: 99%

“…Neurophysiological changes within the nucleus accumbens have been shown in Clock-⌬19 mice (Dzirasa et al, 2010), which may account for their hyperactive phenotype. The same group reported abnormal functional interactions in the mPFC-amygdala circuit in a mouse model of 5-HT deficiency with depressivelike behavior (Dzirasa et al, 2013). Analogously, it would be interesting to test whether 5-HT depletion is accompanied by modifications in specific neural circuits.…”

Section: Fl/ϫmentioning

confidence: 99%

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Behavioral and Physiological Consequences of Adult Brain 5-HT Depletion in Mice

Casanova

2017

J. Neurosci.

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Review of Whitney et al.Serotonergic neurons from the dorsal raphe innervate the amygdala, the mPFC, and the hippocampus, suggesting they have a substantial role in the modulation of emotional states (Lowry et al., 2005). Consistent with this hypothesis, serotonin (5-HT) dysfunction is a key feature of several psychiatric disorders. Therefore, expanding our understanding of the serotonergic system may provide insight into the mechanisms underlying these diseases.Animal models are useful in revealing how circuits, physiology, and behavior are affected by 5-HT depletion. Several of these models involve pharmacological or genetic manipulation of two rate-limiting enzymes involved in 5-HT biosynthesis: tryptophan hydroxylase (Tph) and aromatic amino acid decarboxylase (AADC). Tph converts the amino acid tryptophan to 5-HT, which is then converted to 5-HT by AADC. Although such models have provided valuable insight into 5-HT functions, most of the methods used to date have been difficult to interpret because 5-HT was depleted in the periphery, as well as in the brain tissue, because other monoamine signaling pathways were also affected or because 5-HT was depleted throughout development rather than selectively in adult neurons.To avoid these problems, Whitney et al. (2016) developed a new strategy for depleting 5-HT selectively in the serotonergic ascending pathway of adult mice. Briefly, they injected adeno-associated virus-expressing Cre recombinase (AAV-Cre) into the serotonergic anterior raphe nuclei of mice in which the brain-specific Tph isoform, Tph2, was flanked by loxP sites (Tph2 fl/fl and Tph2 fl/Ϫ). This allowed deletion of Tph2 selectively in the serotonergic nuclei. This method almost completely eliminated Tph2 and 5-HT immunoreactivity in the dorsal raphe nucleus. Importantly, AADC, norepinephrine, and dopamine levels were unaffected, at least at 2 weeks after injection.The disruption of the 5-HT machinery selectively in serotonergic neurons not only confirmed previous findings regarding its role in sleep-wake cycles and locomotor activity (Alenina et al., 2009), but also revealed novel physiological and behavioral consequences. Although classical measures of anxiety-like behavior (i.e., time spent in bright/unprotected vs dark/ protected areas) were not affected by 5-HT depletion, a marked increase in locomotor activity in the open field was found. Moreover, compared with control, 5-HT-depleted mice spent less time in inactive behaviors in the home cage and more time in active behaviors during both the active (dark) and inactive (light) phase of the day. These data rule out the noveltyinduced hyperlocomotion and indicate a hyperactive phenotype. Furthermore, 5-HT-depleted mice showed also an advanced onset and a delayed offset of their daily activity, suggesting alteration in their circadian activity pattern. Average activity time across the day showed that, although overall activity of 5-HT-depleted mice was increased, it was significantly higher only at specific times, confirming that the increase i...

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supporting

confidence: 84%

Section: Fl/ϫmentioning

confidence: 99%

Section: Fl/ϫmentioning

confidence: 99%

Section: Fl/ϫmentioning

confidence: 99%

Section: Fl/ϫmentioning

confidence: 99%

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Behavioral and Physiological Consequences of Adult Brain 5-HT Depletion in Mice

Casanova

2017

J. Neurosci.

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Serotonin depletion eliminates sex differences with respect to context-conditioned immobility in rat

2016

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The microbiome: stress, health and disease

et al. 2013

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Bacterial colonisation of the gut plays a major role in postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Individually, these systems have been implicated in the neuropathology of many CNS disorders and collectively they form an important bidirectional pathway of communication between the microbiota and the brain in health and disease. Regulation of the microbiome-brain-gut axis is essential for maintaining homeostasis, including that of the CNS. Moreover, there is now expanding evidence for the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. Research has focused on how the microbiota communicates with the CNS and thereby influences brain function. The routes of this communication are not fully elucidated but include neural, humoral, immune and metabolic pathways. This view is underpinned by studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics which indicate a role for the gut microbiota in the regulation of mood, cognition, pain and obesity. Thus, the concept of a microbiome-brain-gut axis is emerging which suggests that modulation of the gut microflora may be a tractable strategy for developing novel therapeutics for complex stress-related CNS disorders where there is a huge unmet medical need.

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Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat

Abstract: Serotonin depletion abolishing the sex differences observed at baseline supports the theory that serotonin aids to uphold certain sex differences in behaviour.

Cited by 25 publications

References 60 publications

Behavioral and Physiological Consequences of Adult Brain 5-HT Depletion in Mice

Behavioral and Physiological Consequences of Adult Brain 5-HT Depletion in Mice

Serotonin depletion eliminates sex differences with respect to context-conditioned immobility in rat

The microbiome: stress, health and disease

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