title: The Deakin/Graeff hypothesis: focus on serotonergic inhibition of panic.
abstract: The Deakin/Graeff hypothesis proposes that different subpopulations of serotonergic neurons through topographically organized projections to forebrain and brainstem structures modulate the response to acute and chronic stressors, and that dysfunction of these neurons increases vulnerability to affective and anxiety disorders, including panic disorder. We outline evidence supporting the existence of a serotonergic system originally discussed by Deakin/Graeff that is implicated in the inhibition of panic-like behavioral and physiological responses. Evidence supporting this panic inhibition system comes from the following observations: (1) serotonergic neurons located in the 'ventrolateral dorsal raphe nucleus' (DRVL) as well as the ventrolateral periaqueductal gray (VLPAG) inhibit dorsal periaqueductal gray-elicited panic-like responses; (2) chronic, but not acute, antidepressant treatment potentiates serotonin's panicolytic effect; (3) contextual fear activates a central nucleus of the amygdala-DRVL/VLPAG circuit implicated in mediating freezing and inhibiting panic-like escape behaviors; (4) DRVL/VLPAG serotonergic neurons are central chemoreceptors and modulate the behavioral and cardiorespiratory response to panicogenic agents such as sodium lactate and CO2. Implications of the panic inhibition system are discussed.
authors.affiliation: Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA. Electronic address: evan.paul@colorado.edu.
authors.forename: Evan D
authors.initials: ED
authors.lastname: Paul
authors.affiliation: Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA. Electronic address: philjohn@iupui.edu.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Johnson
authors.affiliation: Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA. Electronic address: ashekhar@iupui.edu.
authors.forename: Anantha
authors.initials: A
authors.lastname: Shekhar
authors.affiliation: Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA. Electronic address: christopher.lowry@colorado.edu.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007266:Inhibition, Psychological; D010200:Panic / Q000502:physiology*; D016584:Panic Disorder / Q000150:complications / Q000453:epidemiology / Q000473:pathology*; D012120:Respiration Disorders / Q000209:etiology; D059326:Serotonergic Neurons / Q000502:physiology*
keywords: Acid-sensing ion channels; Amygdala; Carbon dioxide; Corticotropin-releasing hormone; Dorsal raphe nucleus; Panic attack; Panic disorder; Periaqueductal gray; Serotonin; Sodium lactate; Stress; TASK