Serotonin in panic disorder and social phobia

Sheehan, David V.; Raj, B. Ashok; Trehan, R. R.; Knapp, E.

doi:10.1097/00004850-199311002-00010

Cited by 51 publications

(20 citation statements)

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“…Selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for anxiety disorders (Rickels and Rynn, 2002;Sheehan et al, 1993). The novelty-induced hypophagia test is currently the only behavioral paradigm in mice sensitive to the selective anxiolytic effect of chronic, but not acute, antidepressant treatment (Dulawa and Hen, 2005).…”

Section: Pharmacological Treatment Of Elevated Anxiety With Chronic Ementioning

confidence: 99%

A Functional Tph2 C1473G Polymorphism Causes an Anxiety Phenotype via Compensatory Changes in the Serotonergic System

Berger

Weber

Perreau-Lenz

et al. 2012

Neuropsychopharmacol

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The association of single-nucleotide polymorphisms (SNPs) in the human tryptophan hydroxylase 2 (TPH2) gene with anxiety traits and depression has been inconclusive. Observed inconsistencies might result from the fact that TPH2 polymorphisms have been studied in a genetically heterogeneous human population. A defined genetic background, control over environmental factors, and the ability to analyze the molecular and neurochemical consequences of introduced genetic alterations constitute major advantages of investigating SNPs in inbred laboratory mouse strains. To investigate the behavioral and neurochemical consequences of a functional C1473G SNP in the mouse Tph2 gene, we generated congenic C57BL/6N mice homozygous for the Tph2 1473G allele. The Arg 447 substitution in the TPH2 enzyme resulted in a significant reduction of the brain serotonin (5-HT) in vivo synthesis rate. Despite decreased 5-HT synthesis, we could detect neither a reduction of brain region-specific 5-HT concentrations nor changes in baseline and stress-induced 5-HT release using a microdialysis approach. However, using a [ 35 S]GTP-g-S binding assay and 5-HT 1A receptor autoradiography, a functional desensitization of 5-HT 1A autoreceptors could be identified. Furthermore, behavioral analysis revealed a distinct anxiety phenotype in homozygous Tph2 1473G mice, which could be reversed with chronic escitalopram treatment. Alterations in depressive-like behavior could not be detected under baseline conditions or after chronic mild stress. These findings provide evidence for an involvement of functional Tph2 polymorphisms in anxiety-related behaviors, which are likely not caused directly by alterations in 5-HT content or release but are rather due to compensatory changes during development involving functional desensitization of 5-HT 1A autoreceptors.

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Section: Pharmacological Treatment Of Elevated Anxiety With Chronic Ementioning

confidence: 99%

A Functional Tph2 C1473G Polymorphism Causes an Anxiety Phenotype via Compensatory Changes in the Serotonergic System

Berger

Weber

Perreau-Lenz

et al. 2012

Neuropsychopharmacol

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“…These include anxiety disorders such as general anxiety disorder, social phobia, panic, and obsessive compulsive disorder (Norman et al, 1989;Grae et al, 1997;Sheehan et al, 1993); schizophrenia (Iqbal and van Praag, 1995); eating disorders (Brewerton, 1995), sleep and chronobiological disorders (Jacobs, 1994); autism and developmental disorders (McBride et al, 1990); aggressive and impulse control (Olivier et al, 1995); alcoholism (Linnoila et al, 1998;Sellers et al, 1997); ageing and neurodegeneration (Gottfries, 1991); substance abuse (Tyers and Hayes, 1992;Grant, 1995) and pain sensitivity (Sawynok, 1997). However, it is perhaps the role of this indoleamine in both the pathogenesis of depression and in the mechanism of action of antidepressants that has received the most attention and on which this review is focused.…”

Section: -Ht and Psychiatry: Four Generations Of Progressmentioning

confidence: 99%

5-HT1A and beyond: the role of serotonin and its receptors in depression and the antidepressant response

Cryan

Leonard

2000

Hum. Psychopharmacol. Clin. Exp.

146

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Since its discovery 50 years ago, the role of the indoleamine 5-HT (5-hydroxytryptamine; serotonin) in the pathogenesis of depression and in the mechanism of action of antidepressant drugs has been the subject of considerable research. Advances in molecular biology and radioligand techniques have led to the functional characterisation of at least 14 serotonin receptor subtypes. This classification has led to the development of selective compounds that have aided in the efforts of dissecting the complex role of 5-HT in depression and in mediating the antidepressant response. This review focuses largely on novel strategies of targeting specific 5-HT receptors subtypes, especially the presynaptic 5-HT(1A) and 5-HT(1B/1D) receptors. These subtypes are of primary importance in that they control the firing of the 5-HT neuron and the release of 5-HT. In addition, a number of postsynaptic 5-HT receptors have been shown to be dysfunctional in depression and are also potential targets for a number of antidepressants. We conclude that selective targeting of 5-HT receptors may lead to a faster acting and more efficient antidepressant response. Copyright 2000 John Wiley & Sons, Ltd.

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“…Besides being one of the most widely prescribed drugs for depression, fluoxetine (FLX) is also used for anxiety-related disorders such as obsessive-compulsive disorder, panic, social phobia and bulimia nervosa (1)(2)(3)(4)(5). However, the classic hypothesis relating increased serotonergic function to anxiety (6,7) predicts that fluoxetine, a selective serotonin reuptake inhibitor (SSRI), would provoke an anxiogenic effect when tested on animal models.…”

Section: Introductionmentioning

confidence: 99%

Anxiogenic-like effect of acute and chronic fluoxetine on rats tested on the elevated plus-maze

Silva

Alves

Santarem

1999

Braz J Med Biol Res

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The selective serotonin reuptake inhibitor fluoxetine (FLX) is widely prescribed for depression and anxiety-related disorders. On the other hand, enhanced serotonergic transmission is known to be classically related to anxiety. In this study, the effects of acute (5.0 mg/kg) and chronic (5.0 mg/kg, 22 days) FLX were investigated in both fooddeprived and non-deprived rats tested in the elevated plus-maze. Significant main effects of the three factors (drug, food condition and administration regimen) were observed, but no interaction between them. The administration of either acute or chronic FLX resulted in an anxiogenic effect, as detected by a significant reduction in the percentage of time spent in the open arms and in the percentage of open arm entries. Food deprivation yielded an anxiolytic-like profile, probably related to changes in locomotor activity. The administration regimen resulted in an anxiolytic profile in chronically treated rats, as would be expected after 22 days of regular handling. The anxiogenic action of acute FLX is consistent with both its neurochemical and clinical profile. The discrepancy between the anxiogenic profile of chronic FLX and its therapeutic uses is discussed in terms of possible differences between the type of anxiety that is measured in the plus-maze and the types of human anxiety that are alleviated by fluoxetine.

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Serotonin in panic disorder and social phobia

Cited by 51 publications

References 1 publication

A Functional Tph2 C1473G Polymorphism Causes an Anxiety Phenotype via Compensatory Changes in the Serotonergic System

A Functional Tph2 C1473G Polymorphism Causes an Anxiety Phenotype via Compensatory Changes in the Serotonergic System

5-HT1A and beyond: the role of serotonin and its receptors in depression and the antidepressant response

Anxiogenic-like effect of acute and chronic fluoxetine on rats tested on the elevated plus-maze

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