For example, sensing one’s heartbeat may be misinterpreted as an impending heart attack, triggering uncontrolled fear (reviewed in ref 4). (ii) Other theories focus on ventilation. Klein’s false suffocation alarm theory highlights the similarities between panic attacks

and the powerful fear that suffocation evokes; this theory posits that a “suffocation alarm” is falsely triggered, thus inadvertently producing panic.5 Interestingly, patients with a history of respiratory Inhibitors,research,lifescience,medical disease have a greater risk of panic disorder than the general population.6-8 Similarly, panic disorder patients with prominent respiratory symptoms were more likely to have a prior history of respiratory insult.9 Thus, previous experience and adaptive plasticity and/or conditioning might play a role in panic.13 (iii) Growing knowledge of the anatomy underlying fear conditioning led Gorman and others to speculate that a

Inhibitors,research,lifescience,medical supercharged fear circuit could produce panic in response to a wide variety of arousing stimuli.14,15 This fear circuit is thought to include at least 5 components: (i) Sensory input from viscera via the nucleus of the solitary tract and sensory thalamus, (ii) Processing Inhibitors,research,lifescience,medical and conscious control via the prefrontal cortex, cingulate cortex, and insula. (iii) Processing context and fear through the hippocampus and amygdala, (iv) Coordinated output of behavioral, autonomic, and neuroendocrine manifestations Inhibitors,research,lifescience,medical from the amygdala via the hypothalamus, periacqueductal gray, locus coeruleus, and parabrachial nucleus.14,16 (v) modulation by monoamines including serotonin and the raphe nuclei.14 Supporting this final component is the well-established benefit of selective serotonin reuptake inhibitors. Crucial advances might be made if panic attacks could be evoked in the laboratory Inhibitors,research,lifescience,medical so that the underlying mechanisms might be deconstructed. This review discusses progress based on this approach, which raises the possibility that brain pH and pH-sensitive receptors

may contribute Endonuclease to the pathophysiology of panic disorder. Panic provocation Provocation FK228 challenges offer potential for unique insights into panic Panic disorder is relatively unique among psychiatric illnesses, in that symptoms resembling the illness can be provoked by a number of chemicals called panicogens. Because naturally occurring panic attacks are unpredictable, the ability to induce an attack becomes a powerful tool for research. Moreover, the biological mechanisms of the panicogens themselves might tell us a lot about the neurobiology of the illness. Therefore, it has long been hoped that provocation challenges might shed light on the mechanisms underlying panic.