Validating the inhalation of 7.5% CO2 in healthy volunteers as a human experimental medicine: a model of generalized anxiety disorder (GAD)

@article{Bailey2011ValidatingTI,
  title={Validating the inhalation of 7.5\% CO2 in healthy volunteers as a human experimental medicine: a model of generalized anxiety disorder (GAD)},
  author={Jayne E. Bailey and Gerard R. Dawson and Colin T. Dourish and David J. Nutt},
  journal={Journal of Psychopharmacology},
  year={2011},
  volume={25},
  pages={1192 - 1198}
}
Anxiety is a complex phenomenon that can represent contextually different experiences to individuals. The experimental modelling in healthy volunteers of clinical anxiety experienced by patients is challenging. Furthermore, defining when and why anxiety (which is adaptive) becomes an anxiety disorder (and hence maladaptive) is the subject of much of the published literature. Observations from animal studies can be helpful in deriving mechanistic models, but gathering evidence from patients and… 
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Pharmacotherapy in Generalized Anxiety Disorder: Novel Experimental Medicine Models and Emerging Drug Targets
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Responses to CO2 challenge was related to task-evoked functional connectivity between regions known to be important in processing potential threat, and measures of functional connectivity within emotional processing networks could be potential biomarkers to enable stratification of healthy volunteers.
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The pharmacological properties of two NK1 antagonists were studied in comparison with a benzodiazepine during a 7% CO2 challenge in a population of healthy volunteers selected for a high sensitivity to the challenge, showing a significant reduction in anxiety assessed on the VAS-A scale and alprazolam significantly attenuated the PSL III-R total score.
Preliminary evidence of anxiolytic effects of the CRF1 receptor antagonist R317573 in the 7.5% CO2 proof-of-concept experimental model of human anxiety
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It is shown that a drug that acts to inhibit the CRF1 receptor shows efficacy in the 7.5% CO2 model of anxiety in healthy participants and is comparable with those effective in preclinical models.
Inhalation of 7.5% carbon dioxide increases alerting and orienting attention network function
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Evidence that CO2 modulates attention mechanisms involved in the temporal detection and spatial location of salient stimuli converges with evidence thatCO2 triggers fear behaviour in animals via direct innervation of a distributed neural network that facilitates environmental hypervigilance.
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References

SHOWING 1-10 OF 46 REFERENCES
A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers
TLDR
It is shown that this CO2 model of anxiety is sensitive to lorazepam and to a lesser extent paroxetine, which gives support to its utility as an experimental model of general anxiety disorder in healthy volunteers.
Effects of 7.5% CO2 challenge in generalized anxiety disorder
TLDR
It is shown that 20 min of 7.5% CO2 gas inhalation increases anxiety responses in patients with generalized anxiety disorder, and this is reliable over time.
Characterization of a 7% carbon dioxide (CO2) inhalation paradigm to evoke anxiety symptoms in healthy subjects
TLDR
Characterizing the carbon dioxide (CO2) procedure in healthy subjects to achieve reliable provocation of anxiety symptoms indicates that the test can be suitable for testing putative anti-panic or anxiolytic drugs in clinical studies using a within subject, crossover design.
The effects of single dose anxiolytic medication on the CO2 models of anxiety: differentiation of subjective and objective measures
TLDR
The lack of anxiolytic actions of propranolol, despite a significant reduction in heart rate, is a further support for a central action of CO2 to produce anxiety.
Preliminary evidence of anxiolytic effects of the CRF1 receptor antagonist R317573 in the 7.5% CO2 proof-of-concept experimental model of human anxiety
TLDR
It is shown that a drug that acts to inhibit the CRF1 receptor shows efficacy in the 7.5% CO2 model of anxiety in healthy participants and is comparable with those effective in preclinical models.
Acute panic inventory symptoms during CO2 inhalation and room‐air hyperventilation among panic disorder patients and normal controls
TLDR
While univariate analyses indicated that many symptoms distinguished between panic and no panic outcome, logistic regression revealed that group differences were subsumed under a few prominent symptoms, namely, fear in general, confusion, dizziness, twitching/trembling, and dyspnea.
A comparison of the effects of a subtype selective and non-selective benzodiazepine receptor agonist in two CO2 models of experimental human anxiety
TLDR
Results show that zolpidem shows some anxiolytic efficacy in the 7.5% CO2 model, similar to alprazolam, and this is the first report of such an effect of zolPidem in a model of anxiety, suggesting a definite role of the GABA-A receptor in CO2-induced anxiety.
Lactate infusion induces panic attacks in patients with premenstrual syndrome.
TLDR
Although cardiovascular responses to lactate were similar among PMS patients regardless of the presence of concomitant anxiety/mood disorders, both plasma cortisol levels and panic and mood scores were higher during the test in those patients with conComitant panic disorder.
Development of CRF1 Receptor Antagonists as Antidepressants and Anxiolytics
TLDR
Although additional research is needed to fully investigate the efficacy and safety profiles of CRF1 receptor antagonists as candidate medications for these disorders, the results of preclinical experiments and clinical trials are encouraging.
GABA-A receptors and the response to CO2 inhalation — A translational trans-species model of anxiety?
  • J. Bailey, D. Nutt
  • Psychology, Biology
    Pharmacology Biochemistry and Behavior
  • 2008
...
1
2
3
4
5
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