Anxiety is a psychological, physiological, and behavioralstate induced in animals and humans by a threat to well-being or survival, either actual or potential. It is character-ized by increased arousal, expectancy, autonomic and neu-roendocrine activation, and specific behavior patterns. Thefunction of these changes is to facilitate coping with anadverse or unexpected situation. Pathological anxiety inter-feres with the ability to cope successfully with life chal-lenges. Vulnerability to psychopathology appears to be aconsequence of predisposing factors (or traits), which resultfrom numerous geneenvironment interactions duringdevelopment (particularly during the perinatal period) andexperience (life events). In this review, the biology of fearand anxiety will be examined from systemic (brainbehav-ior relationships, neuronal circuitry, and functional neu-roanatomy) and cellular/molecular (neurotransmitters, hor-mones, and other biochemical factors) points of view, withparticular reference to animal models. These models havebeen instrumental in establishing the biological correlatesof fear and anxiety, although the recent development ofnoninvasive investigation methods in humans, such as thevarious neuroimaging techniques, certainly opens newavenues of research in this field. Our current knowledgeof the biological bases of fear and anxiety is alreadyimpressive, and further progress toward models or theo-ries integrating contributions from the medical, biological,and psychological sciences can be expected.Dialogues Clin Neurosci. 2002;4:231-249.n a book published in 1878 (Physiologie despassions), Charles Letourneau, who was contemporarywith the French neuroanatomist Paul Broca, definedemotions as passions of a short duration and describeda number of physiological signs and behavioral responsesassociated with strong emotions.1 Emotions are inti-mately linked with organic life, he said, and either resultin an abnormal excitation of the nervous network,which induces changes in heart rate and secretions, orinterrupt the normal relationship between the periph-eral nervous system and the brain. Cerebral activity isfocused on the source of the emotion; voluntary musclesmay become paralyzed and sensory perceptions may bealtered, including the feeling of physical pain. This firstphase of the emotional response is followed by a reac-tive phase, where muscles come back into action, but theattention still remains highly focused on the emotionalsituation. With the knowledge of brain physiology andanatomy that was available at the end of the 19th cen-tury, hypotheses on the mechanisms possibly involved inemotions were of course limited. However, Letourneauassumed that the strong cerebral excitation thataccompanies emotions probably only concerned cer-tain groups of conscious cells in the brain and mustnecessitate a considerable increase of blood flow in thecell regions involved.1 He also mentioned that theintensity, the expression, and the pathological conse-quences of emotions were directly linked to tempera-ments (which he defined within the four classicHippocratic categories).S t a t e o f t h e a r t2 3 1The biology of fear- and anxiety-related behaviorsThierry Steimer, PhDKeywords: anxiety; fear; emotions; animal models; neurobiology; behaviorAuthor affiliations: Clinical Psychopharmacology Unit, Geneva UniversityHospital, Chêne-Bourg, SwitzerlandAddress for correspondence: Unité de Psychopharmacologie Clinique,Domaine de Belle-Idée, 2, chemin du Petit-Bel-Air, CH-1225 Chêne-Bourg,Switzerland(e-mail: thierry.steimer@hcuge.ch)I