Reduced Serotonin-1A Receptor Binding in Social Anxiety Disorder

Lanzenberger, Rupert; Mitterhauser, Markus; Spindelegger, Christoph; Wadsak, Wolfgang; Klein, Nikolas; Mien, Leonhard‐Key; Holik, A.; Attarbaschi, T.; Mossaheb, Nilufar; Sacher, Julia; Geiss-Granadia, Thomas; Kletter, Kurt; Kasper, Siegfried; Tauscher, Johannes

doi:10.1016/j.biopsych.2006.05.022

Cited by 262 publications

(198 citation statements)

References 79 publications

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“…A receptor binding study using positron emission tomography confirmed that postsynaptic 5HT 1A receptor levels were reduced in untreated anxiety patients compared with controls (Lanzenberger et al, 2007). Interestingly, a recent study demonstrated a positive correlation between theta rhythms generated during locomotion and the anxiety level in 5HT 1A Ϫ/Ϫ mice (Gordon et al, 2005).…”

Section: Discussionmentioning

confidence: 84%

Phospholipase C β4 in the Medial Septum Controls Cholinergic Theta Oscillations and Anxiety Behaviors

Shin

Gangadharan²,

Kim³

et al. 2009

J. Neurosci.

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Anxiety is among the most prevalent and costly diseases of the CNS, but its underlying mechanisms are not fully understood. Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manifestations. We found that the mutant mouse for phospholipase C ␤4 (PLC-␤4 Ϫ/Ϫ ) showed attenuated theta rhythm and increased anxiety, presenting the first animal model for the human condition. PLC-␤4 is abundantly expressed in the medial septum, a region implicated in anxiety behavior. RNA interference-mediated PLC-␤4 knockdown in the medial septum produced a phenotype similar to that of PLC-␤4 Ϫ/Ϫ mice. Furthermore, increasing cholinergic signaling by administering an acetylcholinesterase inhibitor cured the anomalies in both cholinergic theta rhythm and anxiety behavior observed in PLC-␤4 Ϫ/Ϫ mice. These findings suggest that (1) PLC-␤4 in the medial septum is involved in controlling cholinergic theta oscillation and (2) cholinergic theta rhythm plays a critical role in suppressing anxiety. We propose that defining the cholinergic theta rhythm profile may provide guidance in subtyping anxiety disorders in humans for more effective diagnosis and treatments.

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Section: Discussionmentioning

confidence: 84%

Phospholipase C β4 in the Medial Septum Controls Cholinergic Theta Oscillations and Anxiety Behaviors

Shin

Gangadharan²,

Kim³

et al. 2009

J. Neurosci.

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show abstract

“…Furthermore, our experiments identified specific misregulated genes probably involved in these behavioural alterations. In particular, the changes in 5-HT1A receptor expression are considered an important determinant of predisposition to mental illness 33 and, although the mechanisms underlying the variable expression of this locus between individuals remain unclear, transcriptional dysregulation has been suggested as a probable candidate 34 . 5-HT2A and 5-HT1B receptors are also of great relevance for behavioural disorders 35,36 .…”

Section: Discussionmentioning

confidence: 99%

Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction

et al. 2014

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The interior of the neuronal cell nucleus is a highly organized three-dimensional (3D) structure where regions of the genome that are linearly millions of bases apart establish sub-structures with specialized functions. To investigate neuronal chromatin organization and dynamics in vivo, we generated bitransgenic mice expressing GFP-tagged histone H2B in principal neurons of the forebrain. Surprisingly, the expression of this chimeric histone in mature neurons caused chromocenter declustering and disrupted the association of heterochromatin with the nuclear lamina. The loss of these structures did not affect neuronal viability but was associated with specific transcriptional and behavioural deficits related to serotonergic dysfunction. Overall, our results demonstrate that the 3D organization of chromatin within neuronal cells provides an additional level of epigenetic regulation of gene expression that critically impacts neuronal function. This in turn suggests that some loci associated with neuropsychiatric disorders may be particularly sensitive to changes in chromatin architecture.

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“…It can be noted that social interaction seems especially sensitive to DRN 5-HT manipulations (e.g., [9,34]) and to peripheral 5-HT treatments after different inescapable stress procedures [16,17]. Furthermore, reduced binding of the 5-HT1A autoreceptor, a biomarker of 5-HT sensitization, within the midbrain raphe has been correlated with social anxiety disorder [20]. These findings parallel the current data in that activation or sensitization of serotonergic cells, as would be the result of low 5-HT1A binding and IS, enhances anxious behavior in a social setting.…”

Section: Discussionmentioning

confidence: 99%

The role of prior stressor controllability and the dorsal raphé nucleus in sucrose preference and social exploration

Christianson

Paul

Irani

et al. 2008

Behavioural Brain Research

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Research investigating how control over stressors affects behavior often utilizes freezing and shuttle escape learning as the behavioral endpoints. These endpoints have been argued to reflect anxious or depressed states, but these descriptions are problematic. The present study sought to determine the impact of stressor controllability and the dorsal raphé nucleus (DRN) on sucrose preference and juvenile social exploration, putative measures of anhedonia and anxiety that are commonly used in studies of stress per se. In Experiment 1 rats were exposed to escapable (ES) or yoked-inescapable (IS) tailshocks. In Experiment 2 ES or IS was given 7 days before all rats received IS. In Experiment 3 the DRN was inactivated during IS by microinjection of 8-OH-DPAT. Sucrose preference and social exploration were tested for several days after stress. A fourth experiment confirmed that juvenile social exploration is sensitive to traditional β-carboline and benzodiazepine manipulations. Both ES and IS reduced sucrose preference, but only IS reduced social exploration. Prior treatment with ES prevented the effect of IS on social exploration but did not prevent the effect of IS on sucrose preference and inactivation of the DRN prevented the effect of IS on social exploration but did not change sucrose preference. The present results indicate that social exploration but not sucrose preference is sensitive to prior stressor controllability, and that DRN activation mediates the effect of IS on social exploration. We argue that DRN-5-HT activation mediates a state of generalized anxiety produced by uncontrollable stress and that juvenile social exploration is a useful behavioral endpoint in stressor controllability studies.

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Reduced Serotonin-1A Receptor Binding in Social Anxiety Disorder

Cited by 262 publications

References 79 publications

Phospholipase C β4 in the Medial Septum Controls Cholinergic Theta Oscillations and Anxiety Behaviors

Phospholipase C β4 in the Medial Septum Controls Cholinergic Theta Oscillations and Anxiety Behaviors

Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction

The role of prior stressor controllability and the dorsal raphé nucleus in sucrose preference and social exploration

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