NDLI: An animal model of panic vulnerability with chronic disinhibition of the dorsomedial/perifornical hypothalamus.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Johnson, Philip L. Shekhar, Anantha
Description	Country affiliation: United States Author Affiliation: Johnson PL ( Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 1111 West 10th Street, Indianapolis, IN 46202, USA.)
Abstract	Panic disorder (PD) is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as sodium lactate infusions or hypercapnia induction. Here we review a model of panic vulnerability in rats involving chronic inhibition of GABAergic tone in the dorsomedial/perifornical hypothalamic (DMH/PeF) region that produces enhanced anxiety and freezing responses in fearful situations, as well as a vulnerability to displaying acute panic-like increases in cardioexcitation, respiration activity and 'flight' associated behavior following subthreshold interoceptive stimuli that do not elicit panic responses in control rats. This model of panic vulnerability was developed over 15 years ago and has provided an excellent preclinical model with robust face, predictive and construct validity. The model recapitulates many of the phenotypic features of panic attacks associated with human panic disorder (face validity) including greater sensitivity to panicogenic stimuli demonstrated by sudden onset of anxiety and autonomic activation following an administration of a sub-threshold (i.e., do not usually induce panic in healthy subjects) stimulus such as sodium lactate, CO(2), or yohimbine. The construct validity is supported by several key findings; DMH/PeF neurons regulate behavioral and autonomic components of a normal adaptive panic response, as well as being implicated in eliciting panic-like responses in humans. Additionally, patients with PD have deficits in central GABA activity and pharmacological restoration of central GABA activity prevents panic attacks, consistent with this model. The model's predictive validity is demonstrated by not only showing panic responses to several panic-inducing agents that elicit panic in patients with PD, but also by the positive therapeutic responses to clinically used agents such as alprazolam and antidepressants that attenuate panic attacks in patients. More importantly, this model has been utilized to discover novel drugs such as group II metabotropic glutamate agonists and a new class of translocator protein enhancers of GABA, both of which subsequently showed anti-panic properties in clinical trials. All of these data suggest that this preparation provides a strong preclinical model of some forms of human panic disorders.
File Format	HTM / HTML
ISSN	00319384
e-ISSN	1873507X
DOI	10.1016/j.physbeh.2012.03.016
Journal	Physiology & Behavior
Issue Number	5
Volume Number	107
Language	English
Publisher	Elsevier
Publisher Date	2012-12-05
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Panic Gabaergic Neurons Hypothalamus Physiopathology Discipline Physiology Panic Disorder Animals Physiology Discipline Behavioral Neuroscience Disease Models, Animal
Content Type	Text
Resource Type	Article
Subject	Experimental and Cognitive Psychology Behavioral Neuroscience

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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