The effect of doxapram on brain imaging in patients with panic disorder

Abstract

Administration of doxapram hydrochloride, a respiratory stimulant, is experienced by panic disorder patients to be similar to panic attacks but has reduced emotional effect in normal volunteers thus providing a laboratory model of panic for functional imaging. Six panic patients and seven normal control subjects underwent positron emission tomography with 18F-deoxyglucose imaging after a single-blinded administration of either doxapram or a placebo saline solution. Saline and doxapram were administered on separate days in counterbalanced order. Patients showed a greater heart rate increase on doxapram from saline than controls, indicating differential response. On the saline placebo day, patients had greater prefrontal relative activity than controls. In response to doxapram, patients tended to decrease prefrontal activity more than controls, and increased cingulate gyrus and amygdala activity more than controls. This suggests that panic disorder patients activate frontal inhibitory centers less than controls which may lower the threshold for panic.

Examining face and construct validity of a noninvasive model of panic disorder in Lister-hooded rats

“…In our last experiment, we confirmed the finding of a previous study (Neophytou et al 2000) that ultrasound exposure increases the number of c-Fos immunoreactive cells selectively in the dPAG and dlPAG, as well as in several amygdaloid subregions, i.e., brain regions strongly associated with human panic attacks (Garakani et al 2007;Graeff and Del-Ben 2008;Schenberg et al 2001;Javanmard et al 1999). In addition, we observed that increases in c-Fos expression in the dPAG and the dlPAG could be prevented by pretreatment with the clinically effective anxiolytic/ panicolytic diazepam at a dose previously shown to significantly and selectivity reduce ultrasound-induced escape behaviors (Nicolas et al 2007).…”

Heart rate and respiratory response to doxapram in patients with panic disorder

“…Doxapram, a respiratory stimulant acting on the carotid body chemoreceptors, has been used in anesthesiology and has the benefit of a rapid onset, short duration, and low blood-brain barrier penetration (Folgering et al, 1981; Calverley, 1983; Hirsh and Wang, 1974; Yost, 2006). Doxapram has been shown to cause panic attacks in patients with PD more often than in HC (Lee et al, 1993; Abelson et al, 1996a,b; Abelson et al, 2007; Fujimura et al, 2009), including studies by our group (Gutman et al, 2005; Kent et al, 2005, Garakani et al, 2007). …”

Cortico-limbic circuitry and the airways: Insights from functional neuroimaging of respiratory afferents and efferents

“…The PET isotope fluorine 18 deoxyglucose (FDG) has a substantially long half-life, which permits the examination of neural activity over a 30 minute period preceding actual image acquisition. Thus, FDG-PET could be used in protocols that involve ambulatory respiratory tasks of long duration, yet few respiratory neuroimaging studies have used FDG-PET (Garakani et al, 2007; Tashiro et al, 2008). ASL-fMRI has also been found to support protocols with significant inter-trial latencies (i.e., minutes to hours) (Wang et al, 2003).…”

“…Despite findings of normal ventilatory response to hypercapnia and hypoxia (Papp et al, 1997; Katzman et al, 2002), PD patients have been shown to consistently demonstrate exaggerated anxiety responses to provocative respiratory stimuli (Abelson et al, 1996; Rassovsky and Kushner, 2003). Garakani et al (2007) measured regional glucose uptake via FDG-PET in PD patients and healthy control subjects during challenge with doxapram, a potent respiratory stimulant with demonstrated efficacy to provoke panic attacks in PD patients. Compared to healthy controls, PD patients demonstrated exaggerated regional glucose uptake in the amygdala, insula, ACC and basal ganglia, but decreased glucose uptake in the DLPFC during doxapram challenge.…”