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Psychopharmacology (Berl). 2008 Aug;199(3):421-37. Epub 2007 Dec 6.

Models and mechanisms of anxiety: evidence from startle studies.

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  • Unit of Affective Psychophysiology, Mood and Anxiety Disorder Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-2670, USA. Christian.grillon@nih.gov



Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by flight or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety).


The objectives of the study are to (1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, (2) describe experimental models of anxiety, as opposed to fear, in humans, (3) examine the relevance of these models to clinical anxiety.


The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to non-phobic anxiety disorders.


Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat.

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