Does the brain noradrenaline network mediate the effects of the CO2 challenge?

The inhalation of carbon dioxide (CO2) is commonly used in patients and volunteers as a means of producing anxiety or panic. It is generally believed that patients with panic disorder are more vulnerable to the effects of CO2 than patients with other anxiety disorders or healthy volunteers and there is speculation and debate as to the mechanism for this apparent sensitivity. Recent work from our group has shown that a single inhalation of 35% CO2 activates the hypothalamic-pituitary-adrenocortical (HPA) axis, increases blood pressure (BP) and increases subjective fear responses in healthy volunteers. Correlation analyses reveal a relationship between the changes in BP and the cortisol increase. These findings led us to postulate that a common mechanism may mediate these and the subjective responses to inhalation of CO2. We propose that the noradrenergic system, particularly the locus coeruleus (LC), but including the A1 and A2 cell groups, may be a key mediator of these responses. This article examines the evidence and discusses the results of studies from our laboratory in relation to a neuroanatomical model centring on the LC.