Since hyperventilation and shortness of breath are characteristic features of panic attacks, and since the attacks can be elicited by CO2 inhalation, an involvement of central or peripheral chemoreceptors in the pathophysiology of panic disorder has been suggested. Prompted by clinical reports suggesting that the susceptibility to spontaneous as well as CO2-induced anxiety and hyperventilation is attenuated by serotonin reuptake inhibitors (SRIs), we undertook the present study in order to explore the possible effect of an SRI, paroxetine, on baseline respiration and CO2-induced hyperventilation in freely moving Wistar rats. A significant increase in baseline respiratory rate was seen both after 5 and 15 weeks of treatment with paroxetine. CO2 exposure induced a dose-dependent increase in respiratory rate, but not tidal volume, in both paroxetine-treated rats and controls; this response was reduced after 15 weeks of paroxetine treatment, but not after 5 weeks of treatment. We suggest that an influence on the regulation of respiration may be of importance for the anti-panic effect of SRIs. (C) 2003 Elsevier B.V./ECNP. All rights reserved.