Brain Circuits Regulated by the 5-HT2A Receptor: Behavioural Consequences on Anxiety and Fear Memory

Moulédous, Lionel; Guiard, Bruno P.

doi:10.1007/978-3-319-70474-6_10

Cited by 5 publications

(5 citation statements)

References 173 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, a study in healthy volunteers using questionnaire measures of neuroticism showed a positive relationship with 5HT 2A BP in frontolimbic areas, including the left but not the right insula (45). Thus, while these studies support the role of cortical 5HT 2A in the regulation of emotion, different brain regions selectively involved in the regulation of distinct aspects of emotional behavior may show specific 5HT 2A functional patterns (46).…”

Section: Discussionmentioning

confidence: 77%

Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates

Santangelo

Sawiak

Fryer

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Genetic variation in the serotonin transporter gene (SLC6A4) is associated with vulnerability to affective disorders and pharmacotherapy efficacy. We recently identified sequence polymorphisms in the common marmoset SLC6A4 repeat region (AC/C/G and CT/T/C) associated with individual differences in anxiety-like trait, gene expression, and response to antidepressants. The mechanisms underlying the effects of these polymorphisms are unknown, but a key mediator of serotonin action is the serotonin 2A receptor (5HT2A). Thus, we correlated 5HT2A binding potential (BP) and RNA gene expression in 16 SLC6A4 genotyped marmosets with responsivity to 5HT2A antagonism during the human intruder test of anxiety. Voxel-based analysis and RNA measurements showed a reduction in 5HT2A BP and gene expression specifically in the right posterior insula of individuals homozygous for the anxiety-related variant AC/C/G. These same marmosets displayed an anxiogenic, dose-dependent response to the human intruder after 5HT2A pharmacological antagonism, while CT/T/C individuals showed no effect. A voxel-based correlation analysis, independent of SLC6A4 genotype, revealed that 5HT2A BP in the adjacent right anterior insula and insula proisocortex was negatively correlated with trait anxiety scores. Moreover, 5HT2A BP in both regions was a good predictor of the size and direction of the acute emotional response to the human intruder threat after 5HT2A antagonism. Our findings suggest that genetic variation in the SLC6A4 repeat region may contribute to the trait anxious phenotype via neurochemical changes in brain areas implicated in interoceptive and emotional processing, with a critical role for the right insula 5HT2A in the regulation of affective responses to threat.

show abstract

Section: Discussionmentioning

confidence: 77%

Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates

Santangelo

Sawiak

Fryer

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The excitatory effect of psilocybin on cortical pyramidal neurons projecting to the dorsal raphe may be responsible for a dose-dependent increase in 5-HT release in the nucleus accumbens. However, 5-HT release from serotonin terminals may also be modulated by 5-HT2A receptors located in GABAergic interneurons in the dorsal raphe cells, but this mechanism seems to be less pronounced since the levels of 5-HT2A receptor mRNA in the dorsal raphe cells are low [ 35 ]. The weaker effect of ketamine on serotonin release as compared to psilocybin may involve NMDA receptors in GABAergic neurons disinhibiting glutamatergic innervation of dorsal raphe cells [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Limbic System Response to Psilocybin and Ketamine Administration in Rats: A Neurochemical and Behavioral Study

Wojtas,

Bysiek,

Wawrzczak-Bargiela

et al. 2023

IJMS

View full text Add to dashboard Cite

The pathophysiology of depression is related to the reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well understood; however, clinical studies have shown that the administration of the fast-acting antidepressant ketamine reversed the decrease in hippocampus and amygdala volume in depressed patients, and the magnitude of this effect correlated with the reduction in depressive symptoms. In the present study, we attempted to find out whether the psychedelic substance psilocybin affects neurotransmission in the limbic system in comparison to ketamine. Psilocybin and ketamine increased the release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of naive rats as demonstrated using microdialysis. Both drugs influenced glutamate and GABA release in the nucleus accumbens, hippocampus and amygdala and increased ACh levels in the hippocampus. The changes in D2, 5-HT1A and 5-HT2A receptor density in the nucleus accumbens and hippocampus were observed as a long-lasting effect. A marked anxiolytic effect of psilocybin in the acute phase and 24 h post-treatment was shown in the open field test. These data provide the neurobiological background for psilocybin’s effect on stress, anxiety and structural changes in the limbic system and translate into the antidepressant effect of psilocybin in depressed patients.

show abstract

“…Serotonin, also known as 5-hydroxytryptamine or 5-HT, is well-known for its role in regulating anxiety and its behavior in both clinical and experimental studies (Moulédous et al, 2018;10.3389/fncel.202310.3389/fncel. .1130505 Abela et al, 2020Zangrossi et al, 2020).…”

Section: Serotoninmentioning

confidence: 99%

The cerebellum and anxiety

Chin

Augustine

2023

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Although the cerebellum is traditionally known for its role in motor functions, recent evidence points toward the additional involvement of the cerebellum in an array of non-motor functions. One such non-motor function is anxiety behavior: a series of recent studies now implicate the cerebellum in anxiety. Here, we review evidence regarding the possible role of the cerebellum in anxiety—ranging from clinical studies to experimental manipulation of neural activity—that collectively points toward a role for the cerebellum, and possibly a specific topographical locus within the cerebellum, as one of the orchestrators of anxiety responses.

show abstract

Brain Circuits Regulated by the 5-HT2A Receptor: Behavioural Consequences on Anxiety and Fear Memory

Cited by 5 publications

References 173 publications

Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates

Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates

Limbic System Response to Psilocybin and Ketamine Administration in Rats: A Neurochemical and Behavioral Study

The cerebellum and anxiety

Contact Info

Product

Resources

About