In patients with panic disorder the anxiety resulting from a CO₂ challenge has been shown to be sensitive to treatment with acute or chronic treatment with the benzodiazepine alprazolam. Although much of the published literature on CO₂ -induced anxiety has focused on panic anxiety in patients with panic disorder researchers at Bristol led by Prof David Nutt have recently reported that the inhalation of 7.5% CO₂ in healthy subjects produces an increase in blood pressure and heart rate, and increased feelings of anxiety, fear and tension (Bailey et al 2005). The model has been validated with the benzodiazepine lorazepam and the results replicated in a number of independent studies. Recently the SSRI paroxetine has also been shown to have positive effects in this model.

Dental phobia affects about 20% of the population leading to dental neglect. Eventually, patients in whom dental neglect results in chronic pain present to hospital dental units where treatment is normally administered under sedation.
Not surprisingly patients with dental phobia have high levels of anxiety on the day of the procedure; which can be effectively reduced by alprazolam. However, recently obtained pilot data suggests that levels of anxiety increase in the days leading up to treatment. These data indicate that anxiety levels begin to increase approximately 3-4 days before the procedure and peak immediately before surgery begins. The advantage of this assay is that the anxiety induced is pathological and chronic with a low signal to noise ratio.

Antidepressants that inhibit the reuptake of serotonin (SSRIs) or noradrenaline are effective in the treatment of disorders such as depression and anxiety. Cognitive theories emphasize the importance of correcting negative biases of information processing in the non-pharmacological treatment of these disorders, but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information. Consequently, researchers in Oxford led by Prof Guy Goodwin have assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers. Forty-two male and female volunteers were randomly assigned to 7 days of double-blind intervention with the SSRI citalopram (20 mg/day), the selective noradrenaline reuptake inhibitor reboxetine (8 mg/day), or placebo. On the final day, facial expression recognition, emotion- potentiated startle response, and memory for affect-laden words were assessed. Questionnaires monitoring mood, hostility, and anxiety were given before and after treatment. In the facial expression recognition task, citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear. Citalopram also abolished the increased startle response found in the context of negative affective images. Both antidepressants increased the relative recall of positive (versus negative) emotional material. These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety. However, reboxetine decreased subjective ratings of hostility and elevated energy. The effects of citalopram on the processing of fear are consistent with a role for the amygdala in SSRI action. The amygdala plays a primary role in the enhanced startle response during fear, largely characterized in animal models, but supported by studies of patients with amygdala damage. Thus fear potentiated startle may provide an alternative method for assessing the action of novel antidepressants.

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