Deep brain stimulation of the dorsal raphe inhibits avoidance and escape reactions and activates forebrain regions related to the modulation of anxiety/panic

Wscieklica, Tatiana; Silva, Mariana S.; Lemes, Jéssica A.; Melo-Thomas, Liana; Céspedes, Isabel Cristina; Viana, Milena de Barros

doi:10.1016/j.bbr.2016.11.054

Cited by 10 publications

(4 citation statements)

References 68 publications

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“…However, we found that the social approach behaviour in mice treated with carbidopa and 5-HTP was associated with activation of serotonergic neurons in both the rostral and midrostrocaudal DRD. This is consistent with evidence demonstrating that serotonergic activation in the rostral DRD is associated with social approach behaviour following fluoxetine treatment (Payet et al, 2018), while deep brain stimulation of the DRD has an anxiolytic effect in rats (Wscieklica et al, 2017). There is considerable evidence suggesting that the DRD subnucleus plays an important role in modulating anxiety-related behaviour (Matthiesen et al, 2020; Spiacci et al, 2012; Spiacci et al, 2016).…”

Section: Discussionsupporting

confidence: 91%

“…Furthermore, serotonin turnover is increased in the striatum in response to both acute and chronic stress, while it is increased in the hippocampus following chronic stress (Browne et al, 2011). In male Wistar rats, deep brain stimulation of the DRD has an anxiolytic effect in the elevated T-maze along with increased activation within the medial amygdala, lateral septum and cingulate cortex (Wscieklica et al, 2017). Taken together, these findings suggest that a forebrain anxiety network likely plays an important role in both social and anxiety-like defensive behaviour.…”

Section: Discussionmentioning

confidence: 99%

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Acute treatment with 5-hydroxytryptophan increases social approach behaviour but does not activate serotonergic neurons in the dorsal raphe nucleus in juvenile male BALB/c mice: A model of human disorders with deficits of sociability

et al. 2022

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Background: The BALB/c mouse has been proposed as a model of human psychiatric disorders characterised by elevated anxiety and altered sociability. Juvenile BALB/c mice show decreased social exploratory behaviour, increased anxiety, and reduced brain serotonin synthesis compared to other strains including C57BL/6J mice. Aim: To determine whether supplementation of brain serotonin synthesis alters social behaviour and activation of serotonergic neurons across subregions of the dorsal raphe nucleus (DR) in BALB/c mice. Methods: Juvenile male BALB/c mice were assigned to one of four treatment conditions: vehicle/vehicle, carbidopa (25 mg/kg)/vehicle, vehicle/5-HTP (10 mg/kg), carbidopa (25 mg/kg)/5-HTP (10 mg/kg). Social behaviour was measured using the three-chamber social approach test, followed by immunohistochemical staining for TPH2 and c-Fos to measure activation of serotonergic neurons across subregions of the DR. Results: Mice treated with carbidopa/5-HTP spent more time in the social cage zone and covered more distance in the social approach test compared to other treatment groups. There was no difference between treatment groups in the activation of serotonergic neurons across subregions of the DR. However, the DRD was associated with increased social approach behaviour in carbidopa/5-HTP treated animals. Conclusions: Supplementation of serotonin synthesis can increase social approach behaviour in juvenile BALB/c mice. An increase in locomotor behaviour was also observed suggesting that increasing central serotonin synthesis may have led to a reduction in state anxiety, manifesting in increased exploratory behaviour. As no effect on serotonergic activation within the DR was found, alternative mechanisms are likely important for the effects of 5-HTP on social behaviour.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Acute treatment with 5-hydroxytryptophan increases social approach behaviour but does not activate serotonergic neurons in the dorsal raphe nucleus in juvenile male BALB/c mice: A model of human disorders with deficits of sociability

et al. 2022

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“…Reduced social interaction time was strongly correlated with tph2 mRNA expression in the DRD core. Furthermore, Ucn1-priming decreased tph2 expression in DRVL/VLPAG serotonergic neurons, a subpopulation of serotonergic neurons that has been implicated in inhibition of panic-like physiological and behavioral responses (Wscieklica et al, 2017;Donner and Lowry, 2013;Hassell Jr et al, 2017). In contrast, Ucn1-priming altered slc6a4 expression in the rostral DRD core, rostral MnR and DRI, regions that are implicated in stress resilience (Paul and Lowry, 2013).…”

Section: Discussionmentioning

confidence: 95%

Crh receptor priming in the bed nucleus of the stria terminalis (BNST) induces tph2 gene expression in the dorsomedial dorsal raphe nucleus and chronic anxiety

Donner¹,

Davies²,

Fitz³

et al. 2020

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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The bed nucleus of the stria terminalis (BNST) is a nodal structure in neural circuits controlling anxiety-related defensive behavioral responses. It contains neurons expressing the stress-and anxiety-related neuropeptide corticotropin-releasing hormone (Crh) as well as Crh receptors. Repeated daily subthreshold activation of Crh receptors in the BNST is known to induce a chronic anxiety-like state, but how this affects neurotransmitter-relevant gene expression in target regions *

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“…Few studies have assessed the effects of ACC neuromodulation for anxiety disorders; however, the future work that better defines the role of the ACC in anxiety may lead to therapeutic breakthroughs. [15,34]…”

Section: Discussionmentioning

confidence: 99%

Elimination of anxiety after laser interstitial thermal ablation of the dominant cingulate gyrus for epilepsy

Anand

Gavvala

Mathura

et al. 2022

Surgical Neurology International

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Background: Anxiety is a common symptom of mental health disorders. Surgical treatment of anxiety-related disorders is limited by our understanding of the neural circuitry responsible for emotional regulation. Limbic regions communicate with other cortical and subcortical regions to generate emotional responses and behaviors toward anxiogenic stimuli. Epilepsy involving corticolimbic regions may disrupt normal neural circuitry and present with mood disorders. Anxiety presenting in patients with mesial temporal lobe epilepsy is common; however, anxiety in patients with cingulate epilepsy is not well described. Neurosurgical cases with rare clinical presentations may provide insight into the basic functionality of the human mind and ultimately lead to improvements in surgical treatments. Case Description: We present the case of a 24-year-old male with a 20-year history of nonlesional and cingulate epilepsy with an aura of anxiety and baseline anxiety. Noninvasive work-up was discordant. Intracranial evaluation using stereoelectroencephalography established the epileptogenic zone in the left anterior and mid-cingulate gyrus. Stimulation of the cingulate reproduced a sense of anxiety typical of the habitual auras. We performed laser interstitial thermal therapy of the left anterior and mid-cingulate gyrus. At 8 months following ablation, the patient reported a substantial reduction in seizure frequency and complete elimination of his baseline anxiety and anxious auras. Conclusion: This case highlights the role of the cingulate cortex (CC) in regulating anxiety. Ablation of the epileptic focus resolved both epilepsy-related anxiety and baseline features.a Future studies assessing the role of the CC in anxiety disorders may enable improvements in surgical treatments for anxiety disorders.

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Deep brain stimulation of the dorsal raphe inhibits avoidance and escape reactions and activates forebrain regions related to the modulation of anxiety/panic

Cited by 10 publications

References 68 publications

Acute treatment with 5-hydroxytryptophan increases social approach behaviour but does not activate serotonergic neurons in the dorsal raphe nucleus in juvenile male BALB/c mice: A model of human disorders with deficits of sociability

Acute treatment with 5-hydroxytryptophan increases social approach behaviour but does not activate serotonergic neurons in the dorsal raphe nucleus in juvenile male BALB/c mice: A model of human disorders with deficits of sociability

Crh receptor priming in the bed nucleus of the stria terminalis (BNST) induces tph2 gene expression in the dorsomedial dorsal raphe nucleus and chronic anxiety

Elimination of anxiety after laser interstitial thermal ablation of the dominant cingulate gyrus for epilepsy

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