5-HT and mechanisms of defence

Deakin, Bill; Graeff, Frederico Guilherme

doi:10.1177/026988119100500414

Cited by 917 publications

(686 citation statements)

References 76 publications

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“…The observation that ATD increased punishment prediction concurs with classic and more recent findings indicating that 5-HT controls the processing of aversive signals (Tye et al, 1977;Iversen, 1984;Deakin and Graeff, 1991;Daw et al, 2002;Cools et al, 2005b;Pezawas et al, 2005;Harmer et al, 2006). More specifically, the selective effect of ATD on punishment prediction is consistent with a recent theoretical model, suggesting that in prediction learning 5-HT acts as a motivational opponent to dopamine, which is commonly implicated in the prediction of future reward (Daw et al, 2002).…”

Section: Discussionsupporting

confidence: 89%

“…In keeping with this hypothesis, recent neuroimaging observations suggest that the PFC controls amygdala activity when subjects are presented with negatively valenced stimuli (Ochsner et al, 2002;Phelps and LeDoux, 2005). Based on previous suggestions that 5-HT conveys resilience to adversity (Deakin and Graeff, 1991;Deakin, 1991;Richell et al, 2005), we hypothesize that ATD disrupts PFC-mediated control over subcortical brain regions, such as the amygdala and/or the dorsal raphe nucleus (Amat et al, 2005;Heinz et al, 2005;Pezawas et al, 2005). Such a top-down control failure may interact with reductions in 'background' levels of tonic 5-HT to bias the system toward anticipation of adversity (by increasing prediction errors for future punishment).…”

Section: Discussionmentioning

confidence: 88%

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Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Cools

Robinson

Sahakian

2007

Neuropsychopharmacol

152

154

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Central serotonin (5-HT) has been implicated in emotional and behavioral control processes for many decades, but its precise contribution is not well understood. We used the acute tryptophan depletion procedure in young healthy volunteers to test the hypothesis that central 5-HT is critical for predicting punishment. An observational reversal-learning task was employed that provided separate measures of punishment and reward prediction. Under baseline, subjects made more prediction errors for punishmentassociated stimuli than for reward-associated stimuli. This bias was abolished after central 5-HT depletion, which enhanced the ability to predict punishment while not affecting reward prediction. The selective potentiation of punishment prediction concurs with recent theorizing, suggesting that central 5-HT carries a prediction error for future punishment, but not for future reward (Daw et al, 2002). Furthermore, the finding highlights the importance of central 5-HT in resilience to adversity and may have implications for a variety of neuropsychiatric disorders including depression and anxiety.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 88%

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Cools

Robinson

Sahakian

2007

Neuropsychopharmacol

152

154

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“…Moreover, previous reports have suggested that there may be an isomorphism between risk assessment in the Mouse Defense Test Battery and several behaviors often described in generalized anxiety disorder patients (Blanchard et al, 1997b) such as apprehensive expectation and vigilance and scanning involving hyper-attentiveness (DSM-IV, 1994). In addition, the observation that panic disorder patients usually report an urgent desire to flee from where the attack is occurring (DSM-IV, 1994), has led to suggestions that panic symptoms are due to pathological, spontaneous activation of neuronal mechanisms underlying flight reactions (Deakin and Graeff, 1991;Graeff, 1990). As such, flight behaviors in the Mouse Defense Test Battery may model certain aspects of panic (Griebel et al, 1996b).…”

Section: The Mouse Defense Test Battery: An Experimental Model Of Difmentioning

confidence: 99%

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

Blanchard

Griebel

Blanchard

2003

European Journal of Pharmacology

258

159

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The Mouse Defense Test Battery was developed from tests of defensive behaviors in rats, reflecting earlier studies of both acute and chronic responses of laboratory and wild rodents to threatening stimuli and situations. It measures flight, freezing, defensive threat and attack, and risk assessment in response to an unconditioned predator stimulus, as well as pretest activity and postthreat (conditioned) defensiveness to the test context. Factor analyses of these indicate four factors relating to cognitive and emotional aspects of defense, flight, and defensiveness to the test context. In the Mouse Defense Test Battery, GABA A -benzodiazepine anxiolytics produce consistent reductions in defensive threat/attack and risk assessment, while panicolytic and panicogenic drugs selectively reduce and enhance, respectively, flight. Effects of GABA A -benzodiazepine, serotonin, and neuropeptide ligands in the Mouse Defense Test Battery are reviewed. This review suggests that the Mouse Defense Test Battery is a sensitive and appropriate tool for preclinical evaluation of drugs potentially effective against defense-related disorders such as anxiety and panic. D

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“…Two opposing hypotheses have been put forth to explain panic phenomena by 5-HTergic dysfunction: 5-HT excess or overactivity (Iversen, 1984;Kahn et al, 1988a, b) and 5-HT deficit or underactivity (Deakin and Graeff, 1991;Bell and Nutt, 1998). The 5-HT excess theory suggests that patients with PD either have an increased level of 5-HT release or a hypersensitivity in postsynaptic 5-HT receptors.…”

Section: Introductionmentioning

confidence: 99%

Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

109

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The essential role of serotonin (5-hydroxytryptamine (5-HT)) system in the neurobiology and pharmacotherapy of panic disorder (PD) continues to be a topic of intensive interdisciplinary research. Interest in the involvement of 5-HT in PD has been fuelled by clinical studies demonstrating that medications increasing the synaptic availability of 5-HT, such as selective 5-HT re-uptake inhibitors, are effective in the treatment of PD. Rival theories of 5-HT deficiency vs excess have attempted to explain the impact of 5-HT function in PD. In the past decade, knowledge of the role of 5-HT in the neurobiology of PD has expanded dramatically due to much new research including experimental, treatment, brain-imaging, and genetic studies. The current review attempts to summarize the new data and their implications. The challenge and treatment studies generally confirm the specific inhibitory influence of 5-HT on panicogenesis. The brainimaging studies in PD patients demonstrate functional and clinically relevant alterations in various elements of 5-HT system affecting the neurocircuitry of panic. The findings of genetic association studies suggest that certain 5-HT-related genes may contribute to the susceptibility to PD; however, these data are rather limited and inconsistent. It appears that, even if not the primary etiological factor in PD, the 5-HT function conveys important vulnerability, as well as adaptive factors. A better understanding of these processes may be critical in achieving progress in the treatment of patients suffering from PD.

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5-HT and mechanisms of defence

Cited by 917 publications

References 76 publications

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

Serotonin Function in Panic Disorder: Important, But Why?

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