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Medicine » Mental and Behavioural Disorders and Diseases of the Nervous System » "New Insights into Anxiety Disorders", book edited by Federico Durbano, ISBN 978-953-51-1053-8, Published: March 20, 2013 under CC BY 3.0 license. © The Author(s).

Chapter 2

Anxiety: An Adaptive Emotion

By Ana G. Gutiérrez-García and Carlos M. Contreras
DOI: 10.5772/53223

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Social recognition and olfactory pathways in rodents. Abbrev. VNO, vomeronasal organ; OE, olfactory epithelium; AOB, accessory olfactory bulb; MOB, main olfactory bulb; MeA, medial amygdala; BST, bed nucleus of the stria terminalis; LS, lateral septal nucleus; MPOA, medial preoptic area; Hipp, hippocampus.
Figure 1. Social recognition and olfactory pathways in rodents. Abbrev. VNO, vomeronasal organ; OE, olfactory epithelium; AOB, accessory olfactory bulb; MOB, main olfactory bulb; MeA, medial amygdala; BST, bed nucleus of the stria terminalis; LS, lateral septal nucleus; MPOA, medial preoptic area; Hipp, hippocampus.
Anatomical representation of emotional memory circuit. Connections between amygdala and hippocampus, modulate the use of memories related to sensorial stimuli. Abbrev.: AOB, accessory olfactory bulb, MOB, main olfactory bulb.
Figure 2. Anatomical representation of emotional memory circuit. Connections between amygdala and hippocampus, modulate the use of memories related to sensorial stimuli. Abbrev.: AOB, accessory olfactory bulb, MOB, main olfactory bulb.
Squematic representation of rhinencephalon in several species. Since on evolution point of view (shaded area), rhinencephalon represents as integrative and primitive framework present in the central nervous system, integrating emotions escential for survivance, such as fear and anxiety.
Figure 3. Squematic representation of rhinencephalon in several species. Since on evolution point of view (shaded area), rhinencephalon represents as integrative and primitive framework present in the central nervous system, integrating emotions escential for survivance, such as fear and anxiety.

Anxiety: An Adaptive Emotion

Ana G. Gutiérrez-García1, 2 and Carlos M. Contreras1, 3

1. Introduction

Anxiety as an adaptive response is a natural emotion that occurs in response to danger and prepares an organism to cope with the environment, playing a critical role in its survival. Among the components of anxiety, the expression of fear may inform other members of the group about the presence of imminent danger (i.e., an alarm cue). The environment is perceived by a filtering process that involves sensorial receptors. While coping with a stressful situation, an individual may simultaneously emit vocalizations, perform movements to escape, freeze, and deliver to the environment chemicals called alarm pheromones. These cues are recognized by the receptor-individual by specific sensory systems located in the legs and antennae in insects and olfactory sensorial systems in other organisms. In mammals, the sensorial information is integrated by anatomical and functional pathways, with the participation of structures related to emotional memory, namely deep temporal lobe structures. Some stimuli are perceived as relevant when they contain relevant meaning according to previous experience and learning. The participation of ventral striatum and prefrontal cortex connections then leads to the selection of an adequate strategy for survival. The perception of these cues by other individuals in the group establishes intraspecies communication and causes striking behavioral responses in the receptor subject, namely anxiety, but the consequence is likely different. While the emitting subject may be in an emergency situation that is perhaps devoid of a solution, the receptor subject may have the chance to cope with the dangerous situation by employing efficacious strategies, depending on previous experience. The aim of this chapter is to review the participation of such anatomical pathways, their neurotransmission systems, and the resulting behavioral patterns.


2. Expression of fear and anxiety as emotions

Emotions are transient events generated in response to some stimuli that produce arousal reactions and changes in motor behavior, subjective feelings, and subsequent changes in behavior [15]. Thus, emotions are cognitive and somatic reactions, with a short duration, to specific environmental stimuli [7]. In the case of an emergency situation, emotions give way to strategies that allow the survival of the individual and, therefore, the species. Emotional processes are crucial for the control of human behavior [15], and a failure in the management of emotions is a common denominator of a wide range of psychiatric disorders [22].

In broad terms, emotions are considered to have two dimensions. The first dimension is equilibrium, in which emotional states range from positive (i.e., happy or safe) to negative (i.e., fear or anger). The consequent behavioral responses depend on emotional states. For example, in a positive emotional state, there is a tendency to approach the stimuli, whereas negative emotional states are associated with aversion, defense, escape, and avoidance. The second dimension is arousal. Both positive and negative emotional states may vary from a relatively quiet attitude to high levels of restlessness [54; 53]. Examples include freezing in a passive attitude or escaping in more proactive coping patterns [20]. Emotions play a role in the daily lives of individuals, enabling them to cope with everyday situations.

Fear is a part of the anxiety syndrome. It consists of a feeling of agitation caused by the presence of imminent danger and may be considered a protective emotion. From an evolutionary point of view, however, its expression is very similar to anxiety as an adaptive emotion. An exception may be posttraumatic stress, an anxiety disorder in which fear is present even in the absence of the stimulus that elicited the original state of anxiety [100]. Notably, fear can be conditioned by various stimuli, and its study from different methodological perspectives has allowed a better comprehension of the underlying neurobiological processes of anxiety.

3. Is anxiety a disease or an adaptive response?

Anxiety comprises two related concepts. First, it is a disease. Second, it is an adaptive response. As a disease, anxiety is a highly disabling pathological condition, involving cognitive, emotional, and physiological disturbances. Its main symptoms include restlessness, increased alertness, motor tension, and increased autonomic activity [2]. In the long-term, the deleterious effects of anxiety on personal capabilities represents a considerable mental health problem. Generalized anxiety disorder is frequently associated with other pathologies, but it may constitute the only symptom in several manifestations, including panic disorder, posttraumatic stress disorder, and obsessive compulsive disorder [2]. It is one of the most common psychiatric disorders, affecting approximately 28% of the general population [49]. In México, as in other countries, it occurs more often in women than in men [64]. Typically, the symptoms last a long time, even when the stimulus has disappeared [100].

Adaptive anxiety may be considered a useful emotion that leads to survival strategies [4]. In this sense, anxiety is a normal emotion that occurs when an individual copes with a potentially dangerous situation, constituting a mechanism for alertness or alarm [41]. In this case, the symptoms of anxiety, which are identical to the pathological condition, disappear once the stressful stimulus disappears. Meanwhile, in most cases, it leads to coping with the emergency situation. As the best strategy is chosen, the probability of ensuring survival increases.

One of the main differences between the two kinds of anxiety is the contingency of the response to the stimulus. Otherwise, pathological anxiety induces positive feedback, in which anxiety generates more anxiety [75] and, notably, spreads to other individuals in the group [88; 24]. The combination of feedback and the spread of anxiety can lead to a collective panic reaction that involves those individuals who surrounded the first individual who experienced anxiety [89], often with fatal results [74; 62]. One very special case is related to caregivers. Observing a state of anxiety that leads to deteriorated social functioning and health is common in caregivers, with undesirable effects in both the caregiver and patient [94]. Therefore, anxiety may be both a disease and an adaptive response that involves shared processes and in some cases may inclusively consist of a continuum.

4. Anxiety is contagious

In the case of anxiety as an adaptive emotion that leads to survival strategies, the spread of anxiety to other individuals in the group may offer warning signs that allow for the protection of other individuals and consequently the group and ultimately the species [6].

Generally, all stimuli derived from the environment initially undergo a sensorial filtering process in sensorial receptors, beginning with parareceptors [8], reaching synaptic relays, and leading to an integrative process that involves anatomical structures related to emotional memory [43], in which comparisons are made with older elements of memory [92]. As the stimulus inputs reach the striatum and cortical structures [43], a selection of the adequate survival strategy is often reached [34]. In turn, connections with motor areas and motoneurons activates skeletal muscles [43], and a motoric response may be observed. Laboratory animals subjected to a stressful situation (e.g., odors from a predator) will emit only a few responses—attacking, freezing, or escaping—no more and no less.

One important aspect is the meaning of the stimuli. Only a portion of all environmental stimuli is perceived as relevant when it contains a specific meaning according to previous experience. Any of these stimuli may potentially contain relevant environmental information, but its relevance arises when it is properly interpreted. The contrast between the present stimuli and previous experience allows predictions to be made about the real presence or absence of danger and selecting the correct coping response [34; 63]. An intriguing aspect is that most studies of the neural and behavioral framework of these types of motor responses have been performed in laboratory animals (i.e., animals that were completely naive of predators before the test). However, some studies in naturally free animals have found similar results [19; 90]. The interpretation is that a neural framework adapted by natural selection is able to respond in some effective way, even in the absence of any previous experience. Therefore, the neural framework allows an initial response to any dangerous situation in the environment, yielding necessarily useful strategies for survival. Choosing the best strategy to cope with such situations depends on experience (i.e., learning).

5. Communication and anxiety

During natural selection and evolution, several organisms have developed strategies that allow different but complementary forms of communication between individuals of the same species. Thus, animal communication includes the emission and reception of signals delivered in the environment, usually following some specific code. Moreover, communication also includes behaviors in the receptor-individual. Success in the detection of cues includes a series of processes that consist of emission of the cue, reception by other individuals, encoding, transmission, and decoding [26].

Notably, special situations, such as emergency situations, involve most of the sensorial systems. A primitive form of communication is body language. In this case, environmental information is detected by the visual system. Insects frequently apparently dance while performing stereotyped movements [33] that apparently carry a message whose meaning is not yet fully understood.

The auditory system is involved in the most complex of these forms of communication. A symbolic language that contains a characteristic syntactic structure is apparently peculiar to the human species [79]. In a more primitive form, nonsyntactic and perhaps only symbolic language is observed in other species [6]. In fact, animal vocalizations are devoid of semantic content (i.e., meaning) but posses some semiotic context that contains symbolic value [16]. The signals generated by animals are used for communication and consist of signs that become messages that are capable of influencing the behavior of other individuals who are also able to respond with species-typical signals by distinguishing its semiotic content. For example, most ultrasonic vocalizations of animals, including rats, are true semiotic signs and represent a useful signal within a communication system [63]. Most of these semiotic signals may represent warning cues that seemingly produce some anxiety responses in other individuals of the same species.

Among the signaling systems, chemical cues that consist of pheromones [48] can cause striking behavioral responses, including anxiety [31; 32], when perceived by other individuals of the group. The opposite is also true. Some pheromones consist of cues that indicate the existence of a safe environment [47; 103] by informing other individuals of the same species about the absence of danger or presence of food. In both cases, an emitting-individual releases substances to the environment that are recognized by the receptor-individual by specific sensory systems located, for example, in the legs and antennae in insects [81] or olfactory sensory system in other organisms, including mammals [58]. Figure 1.

6. Neuroanatomical modeling of emotions

Emotional memory allows an individual to recognize signs from the environment and compare them with past experience as an element of judgment to efficaciously respond to the environment by choosing the best coping strategy [14]. During the first half of the 20th century, researchers were interested in the brain mechanisms of emotional behavior [57], and the original concept of the “limbic system” was gradually abandoned. Instead, the very simple, initial anatomical concept (i.e., hippocampus, one thalamic nuclei, mammillary bodies, and cingulum) was enriched by the inclusion of other deep temporal lobe structures, such as the amygdaloid complex [57], so-called mesolimbic structures [73], and prefrontal and orbitofrontal cortices [100]. All of these anatomical regions share similar neurotransmission systems, namely serotonin, norepinephrine, dopamine, and γ-aminobutyric acid (GABA), among others.


Figure 1.

Social recognition and olfactory pathways in rodents. Abbrev. VNO, vomeronasal organ; OE, olfactory epithelium; AOB, accessory olfactory bulb; MOB, main olfactory bulb; MeA, medial amygdala; BST, bed nucleus of the stria terminalis; LS, lateral septal nucleus; MPOA, medial preoptic area; Hipp, hippocampus.

Some alterations in the serotonergic system are associated with psychiatric disorders, such as depression and schizophrenia [87]. Serotonin (5-hydroxytryptamine [5-HT]) is located primarily in the gastrointestinal tract, but it is also detectable in the central nervous system [29] in areas that are functionally related to many behavioral processes. Its main reservoir in the brain is the dorsal raphe nucleus [40; 78], which, among other projections, sends efferent fibers to several structures related to emotional processing, such as the septum, thalamus, amygdaloid complex, nucleus accumbens, hippocampus, and prefrontal cortex [29; 78]. Although a controversial issue [87], an increase of 5-HT in the synaptic cleft exerts anxiolytic effects in animal models of anxiety, such as the social interaction test, light-dark test, Vogel conflict test, Geller-Seifter conflict test, and ultrasonic vocalizations [10, 65], which have been confirmed by many clinical studies [60].

Norepinephrine is related to many functions, such as attention, the regulation of stress, fear, memory, sleep, and wakefulness [27]. It is synthesized in a small group of cells located in the locus coeruleus that sends efferent fibers parallel to those of 5-HT [40; 27]. Norepinephrine is involved in the secretion of corticotrophin-releasing factor, which stimulates the production of adrenocorticotropic hormone that, in turn, releases corticosterone in the adrenal glands, which is responsible of the metabolic response to stress [100; 67; i.e. an inseparable component of anxiety]. Anxiety is directly related to increased activity of locus coeruleus neurons. Drugs that increase noradrenergic activity also increase anxiety, and drugs that reduce noradrenergic activity reduce anxiety [40, 27]. Limbic and cortical regions innervated by the locus coeruleus are those that are thought to be involved in the elaboration of adaptive responses to stress, such as the typical scheme seen in fearful behavior in cats [1].

γ-Aminobutyric acid is a neurotransmitter distributed throughout the central nervous system and the quintessential inhibitory neurotransmitter [72]. Modulation of the GABAergic system at its receptors [5] is linked to the neurobiological mechanisms that regulate anxiety [72; 70; 86]. Most drugs with affinity for the GABAA receptor produce anxiolysis and sedation [96]. These receptors are detectable in the cerebral cortex, amygdala, hippocampus, and striatum [40], providing the physiological basis for the therapeutic action of anxiolytics [72], including gonadal steroids and neurosteroids [25; 12; 61].

Mesolimbic dopamine is found in the ventral tegmental area and involved in the control of cognition and affect [46]. Dopamine innervation of the medial prefrontal cortex appears to be particularly involved in mild and brief stress processing [21]. In turn, the prefrontal cortex plays a role in working memory, in addition to other brain areas, such as the hippocampus. A critical range of dopamine turnover is necessary to keep the working memory system active and ready for optimal cognitive functioning [42], a situation that is impaired in situations of extreme stress [3]. In summary, the dopamine system is important for general emotional responses, selective information processing, hedonic impact, and reward learning. In a broader sense, dopamine is important for reactivity to perturbations in the environment, which is essential for the ability (or failure) to cope with the environment [73; 99].

Multiple neurotransmission systems participate in the processing of anxiety and coping with the environment. Many other neurotransmitters are involved in the regulation of anxiety, including neuropeptides [91], polypeptides [95], and amino acids [104]. Nonetheless, a common denominator is that almost all of these neurotransmitters are located within the anatomical substrate of emotional memory [99], namely the amygdala complex [83].

The amygdala is composed of many functionally heterogeneous nuclei [56]. The lateral and central nuclei of the amygdala mediate the acquisition and expression of reactive defensive behaviors [59; 69], and the basal nucleus plays a key role in fear expression [38]. The basal amygdala nucleus, together with the lateral nucleus and accessory basal nucleus, integrate the basolateral amygdala [84]. As a whole, an increase in the neuronal firing rate of the basolateral amygdala has been related to fear [76], anxiety [101], emotional learning [17], and Pavlovian conditioning [28]. The basal amygdala nucleus appears to mediate fear-motivated reactions [55] but not conditioned auditory fear responses, such as freezing [69]. The central nucleus of the amygdala projects to various brain structures via the stria terminalis and ventral amygdalofugal pathway. The anatomical circuit responsible for the startle reflex begins in auditory pathways and reaches the central amygdala nucleus [18]. Pathways from the amygdala to lateral hypothalamus are related to peripheral sympathetic responses to stress [45]. Early findings reported that electrical stimulation of the amygdala in cats produced peripheral signs of autonomic hyperactivity and fear-related behavior, commonly seen when the animal attacks or is being attacked [39]. Electrical stimulation of the amygdala in human subjects also produces signs and symptoms of fear and anxiety, namely increased heart rate, blood pressure, and muscle tension, accompanied by subjective sensations of fear and anxiety [9] and an increase in plasma catecholamines [30]. Important reciprocal connections also exist between cortical association areas, the thalamus, and the amygdala, which may account for fear responses [82]. These findings demonstrate that the amygdala plays an important role in conditioned fear and the modulation of peripheral stress responses.

7. Fear and anxiety as a consequence of natural selection

The relationship between mother and child is essential for the survival and normal development of infants [71; 85]. Maternal odors attract and guide neonates to the maternal breast [98]. The role of mothers is to provide a source of nutrition for their offspring, but also to protect them from predators [80; 71]. Maternal odors produce signs of calm. Kittens, pups, and human babies exhibit increased agitation and vocalizations when placed in an unfamiliar environment, but when they return to their nest or stay in close proximity to their mother, they calm down [66; 85]. Amniotic fluid olfaction reduces crying in human babies when they are separated from their mothers [97]. Recently, we analyzed human amniotic fluid, colostrum, and breast milk. Eight fatty acids were consistently found in measurable amounts in these three biological fluids. Both amniotic fluid and a mixture of its fatty acids acted as feeding cues, leading to appetitive behavior [11]. Moreover, both amniotic fluid and a mixture of its fatty acids exerted anxiolytic effects in animal models of anxiety [13]. These findings indicate that a system of protection against anxiety is present during intrauterine life, at least in mammals, suggesting a process of natural selection in which an individual is protected from extreme anxiety, even before birth.

With regard to the opposite process, alarm cues (i.e., pheromones) are released by an animal in threatening situations, informing members of the same species about the presence of danger (e.g., the proximity of a predator; 36). The responses of conspecifics to alarm pheromones include fear, autonomic responses, and freezing [51], increased awareness [35], defensive behavior [52], and an increase in anxiety-like behavior (32; 44; i.e., some behaviors mediated by deep temporal lobe structures). A single exposure to predator odors (i.e., 2,3,5-trimethyl-3-tiazoline) contained in fox feces and cats increased c-fos expression in the lateral septal nucleus and central amygdala [19; 90], among other structures. An arterial spin labeling-based functional magnetic resonance imaging study found that neuronal activity increased in the dorsal periaqueductal gray, superior colliculus, and medial thalamus during alarm pheromone exposure [50]. Exposure to odors from potential predators also elicited fast waves in the dentate gyrus [37] and enhanced long-term potentiation in the dentate gyrus [23]. Both the main and accessory olfactory systems are responsive to 2-heptanone [102]. The medial amygdala nucleus receives indirect inputs from the main olfactory system from the piriform cortex, periamygdaloid cortex, and cortical amygdala nucleus and direct inputs from the accessory olfactory system [92]. The hippocampus also receives odor information from both olfactory systems through entorhinal cortex connections [77]. Herein, neurons from medial and cortical amygdala nuclei are activated in the presence of alarm pheromones [52], and the medial amygdala is involved in the neuronal circuitry associated with memory formation related to odors derived from predators, further leading to the expression of unconditioned and conditioned fear behavior [68; 93]. Figure 2.


Figure 2.

Anatomical representation of emotional memory circuit. Connections between amygdala and hippocampus, modulate the use of memories related to sensorial stimuli. Abbrev.: AOB, accessory olfactory bulb, MOB, main olfactory bulb.

8. Conclusions

Most of the known responses to alarm cues have come from studies in laboratory animals that reproduce and feed under relatively comfortable conditions. They live inside very well controlled facilities, distant from predators and dangerous situations. One may reconsider the concept of the rhinencephalon, an almost forgotten anatomical entity that involves brain structures (Figure 3) related to emotional memory and is present in mammals, reptiles, and birds. The rhinencephalon, at least as a concept, contains one of the primitive sources of capturing information from the environment—the olfactory system. The concept is completed by connections of this sensorial system with deep temporal lobe structures (i.e., emotional memory-related structures). Therefore, the existence of the rhinencephalon in many species suggests that the integration of anxiety responses is a broad, essential characteristic determined by natural selection. In such a case, anxiety as an adaptive response is common to species with a centralized nervous system. Anxiety as an adaptive response is also naturally contained in the brain, and it is expressed even before the organism learns the most efficacious behavioral response.


Figure 3.

Squematic representation of rhinencephalon in several species. Since on evolution point of view (shaded area), rhinencephalon represents as integrative and primitive framework present in the central nervous system, integrating emotions escential for survivance, such as fear and anxiety.

Nature protects the mother and fetus during intrauterine development, in which the development of the fetus occurs in an environment that protects it from anxiety. Especially in mammals, early learning acquired through maternal-infant interactions during the first phase of life and subsequent learning acquired through interactions with dominant members of a given group allow the individual to learn to select the most effective survival strategy, with the participation of prefrontal brain structures.

Consequently, two processes occur. One process depends on the neural framework that will respond even in the absence of any previous experience. The other process is a consequence of learning. Working together, the outcome is the utility of anxiety as an adaptive reaction that contributes to the survival of the species.


The authors thank Michael Arends for revising and editing the English of this manuscript. The preparation of this chapter was partially supported by grants from the Consejo Nacional de Ciencia y Tecnología, México (CONACyT: CB-2006-1, 61741), Universidad Nacional Autónoma de México (UNAM: DGAPA-PAPIIT IN211111-3), and Sistema Nacional de Investigadores (SNI, Exp. AGG-32755 and CMC-754).


1 - E. D Abercrombie, B. L Jacobs, 1987 Microinjected clonidine inhibits noradrenergic neurons of the locus coeruleus in freely moving cats. Neurosci Lett 76 2 203 208
2 - American Psychiatric Association 2000 Diagnostic and statistical manual of mental disorders, 4th edition Washington, DC: American Psychiatric Association.
3 - A. F Arnsten, 2000 Stress impairs prefrontal cortical function in rats and monkeys: role of dopamine D1 and norepinephrine α-1 receptor mechanisms. Prog Brain Res 126 183 192
4 - A. M Becerra-garcía, A. C Madalena, C Estanislau, J. L Rodríguez-rico, H Dias, 2007 Ansiedad y miedo: su valor adaptativo y maladaptaciones Rev Latinoamericana Psicol 39 1 75 81
5 - J Bormann, 2000 The “ABC” of GABA receptors. Trends Pharmacol Sci 21 1 16 19
6 - S. M Brudzynski, 2005 Principles of rat communication: quantitative parameters of ultrasonic calls in rats Behav Genet 35 1 85 92
7 - T. W Buchanan, 2007 Retrieval of emotional memories Psychol Bull 133 5 761 779
8 - N. R Carlson, 2001 Physiology and Behavior 7th edition. Boston: Allyn and Bacon.
9 - D. W Chapman, 1954 Anxiety heart disease Med Bull US Army Eur 11 9 211 216
10 - Y Clement, G Chapouthier, 1998 Biological bases of anxiety. Neurosci Biobehav Rev 22 5 623 633
11 - C. M Contreras, A. G Gutiérrez-García, M. R Mendoza-López, J. F Rodríguez-Landa, B Bernal-Morales, C Díaz-Marte, 2012 Amniotic fluid elicits appetitive responses in human newborns: fatty acids and appetitive responses. Dev Psychobiol in press.
12 - C. M Contreras, M Molina, M Saavedra, L Martínez-Mota, 2000 Lateral septal neuronal firing increases during proestrus-estrus in the rat. Physiol Behav 68 279 284
13 - C. M Contreras, J. F Rodríguez-Landa, A. G Gutiérrez-García, M. R Mendoza-López, R. I García-Ríos, J Cueto-Escobedo, 2011 Anxiolytic-like effects of human amniotic fluid and its fatty acids in Wistar rats Behav Pharmacol 22 655 662
14 - C. M Contreras, A. G Gutiérrez-García, 2010 Emotional memory and chemical communication. In: Benítez-King, G. & Cisneros-Berlanga, C. (eds). The neurobiological sciences applied to psychiatry: from genes, proteins, and neurotransmitters to behavior 171 188 Kerala: Research Signpost.
15 - H Critchley, 2003 Emotion and its disorders Br Med Bull 65 35 47
16 - M Danesi, 1993 Messages and meanings: an introduction to semiotics. Toronto: Canadian Scholars’ Press.
17 - M Davis, P. J Whalen, 2001 The amygdala: vigilance and emotion. Mol Psychiatry 6 13 34
18 - M Davis, 1992 The role of the amygdala in fear and anxiety. Annu Rev Neurosci 15 353 375
19 - H. E Day, C. V Masini, S Campeau, 2004 The pattern of brain c-fos mRNA induced by a component of fox odor, 2,5-dihydro-2,4,5 trimethylthiazoline (TMT), in rats, suggests both systemic and processive stress characteristics. Brain Res 1025 1-2 139 151
20 - S. F De-Boer, J. M Koolhaas, 2003 Defensive buyring in rodents: ethology, neurobiology and psychopharmacology. Eur J Pharmacol 463 1-3 145 161
21 - A. Y Deutch, R. H Roth, 1990 The determinants of stress-induced activation of the prefrontal cortical dopamine system. Prog Brain Res 85 367 402
22 - R. J Dolan, 2002 Emotion, cognition, and behavior. Science 298 5596 1191 1194
23 - H. C Dringenberg, D Oliveira, D Habib, 2008 Predator (cat hair)-induced enhancement of hippocampal long-term potentiation in rats: involvement of acetylcholine. Learn Mem 15 3 112 116
24 - J Elizarrarás-Rivas, J. E Vargas-Mendoza, M Mayoral-García, C Matadamas-Zarate, A Elizarrarás-Cruz, M Taylor, K Agho, 2010 Psychological response of family members of patients hospitalised for influenza A/H1N1 in Oaxaca, Mexico BMC Psychiatry 10 104
25 - A Fernández-Guasti, L Martínez-Mota, E Estrada-Camarena, C. M Contreras, C López-Ruvalcava, 1999 Chronic treatment with desipramine induces an estrous cycle-dependent anxiolytic-like action in the burying behavior, but not in the elevated plus-maze test. Pharmacol Biochem Behav 63 13 20
26 - S Green, P Marler, 1979 The analysis of animal communication. In: Marler, P. & Vandenbergh, J.G. (eds). Social behavior and communication (series title: Handbook of behavioral neurobiology, 3 73 158 New York: Plenum Press.
27 - A. W Goddard, S. G Ball, J Martinez, M. J Robinson, C. R Yang, J. M Russell, A Shekhar, 2010 Current perspectives of the roles of the central norepinephrine system in anxiety and depression Depress Anxiety 27 4 339 350
28 - A. A Grace, J. A Rosenkranz, 2002 Regulation of conditioned responses of basolateral amygdala neurons. Physiol Behav 77 489 493
29 - D. G Grahame-Smith, 1988 Serotonine (5-hydroxytrypatmine, 5-HT) Q J Med 67 3 459 466
30 - L. M Gunne, D. J Reis, 1963 Changes in brain catecholamines associated with electrical stimulation of amygdaloid nucleus. Life Sci 11 804 809
31 - A. G Gutiérrez-García, C. M Contreras, 2002 Algunos aspectos etológicos de la comunicación química en ratas y ratones de laboratorio. Rev Bioméd 13 189 209
32 - A. G Gutiérrez-García, C. M Contreras, M. R Mendoza-López, S Cruz-Sánchez, O García-Barradas, J. F Rodríguez-Landa, B Bernal-Morales, 2006 A single session of emotional stress produces anxiety in Wistar rats Behav Brain Res 167 1 30 35
33 - M Hammer, R Menzel, 1995 Learning and memory in the honeybee. J Neurosci 15 3 Pt 1 1617 30
34 - O Hasson, 1994 Cheating signals J Theor Biol 167 223 238
35 - R Hauser, M Marczak, B Karaszewski, M Wiergowski, M Kaliszan, M Penkowski, G Kernbach-Wighton, Z Jankowski, J Namiesnik, 2008 A preliminary study for identifying olfactory markers for fear in the rat. Lab Anim 37 76 80
36 - R Hauser, M Wiergowski, M Kaliszan, T Gos, G Kernbach-Wighton, M Studniarek, Z Jankowski, J Namiesnik, 2011 Olfactory and tissue markers of fear in mammals including humans. Med Hypotheses 77 1062 1067
37 - V. R Heale, C. H Vanderwolf, M Kavaliers, 1994 Components of weasel and fox odors elicit fast wave bursts in the dentate gyrus of rats Behav Brain Res 63 2 159 165
38 - C Herry, S Ciocchi, V Senn, L Demmou, C Muller, A Lüthi, 2008 Switching on and off fear by distinct neuronal circuits Nature 454 600 606
39 - S. M Hilton, A. W Zbrozyna, 1963 Amygdaloid region for defense reactions and its efferent pathway to the brain stem J Physiol 165 160 173
40 - R Hoehn-saric, 1982 Neurotransmitters in anxiety. Arch Gen Psychiatry 39 6 735 742
41 - D. W Hommer, P Skolnick, S. M Paul, 1987 The benzodiazepine/GABA receptor complex and anxiety. In Meltzer, H.Y. (ed). Psychopharmacology: the third generation of progress 977 983 New York: Raven Press.
42 - B. A Horger, R. H Roth, 1996 The role of mesoprefontal dopamine neurons in stress. Crit Rev Neurobiol 10 395 418
43 - M Hughes, 2004 Olfaction, emotion and the amygdala: arousal-dependent modulation of long-term autobiographical memory and its association with olfaction: beginning to unravel the Proust phenomenon? Premier J Undergraduate Publ Neurosci 1 1 1 58
44 - H Inagaki, Y Kiyokawa, T Kikusui, Y Takeuchi, Y Mori, 2008 Enhancement of the acoustic startle reflex by an alarm pheromone in male rats Physiol Behav 93 606 611
45 - J Iwata, LeDoux, J.E.; Meeley, M.P.; Arneric, S. & Reis, D.J. 1986 Intrinsic neurons in the amygdaloid field projected to by the medial geniculate body mediate emotional responses conditioned to acoustic stimuli. Brain Res 383 1-2 195 214
46 - M Jaber, S. W Robinson, C Missale, M. G Caron, 1996 Dopamine receptors and brain function. Neuropharmacology 35 1503 1519
47 - S Jacob, M. K Mcclintock, 2000 Psychological state and mood effects of steroidal chemosignals in women and men. Horm Behav 37 57 78
48 - P Karlson, M Lüscher, 1959 Pheromones: a new term for a class of biologically active substances. Nature 183 4653 55 56
49 - R. C Kessler, A. M Ruscio, K Shear, H. U Wittchen, 2010 Epidemiology of anxiety disorders. Curr Top Behav Neurosci 2 21 35
50 - M. S Kessler, S Debilly, S Schöppenthau, T Bielser, A Bruns, B Künnecke, M Kienlin, J. G Wettstein, J. L Moreau, C Risterucci, 2012 fMRI fingerprint of unconditioned fear-like behavior in rats exposed to trimethylthiazoline Eur Neuropsychopharmacol 22 3 222 230
51 - T Kikusui, S Takigami, Y Takeuchi, Y Mori, 2001 Alarm pheromone enhances stress-induced hyperthermia in rats Physiol Behav 72 1-2 45
52 - Y Kiyokawa, M Shimozuru, T Kikusui, Y Takeuchi, Y Mori, 2006 Alarm pheromone increases defensive and risk assessment behaviors in male rats Physiol Behav 87 2 383 387
53 - K.S. LaBar, R Cabeza, 2006 Cognitive neuroscience of emotional memory. Nat Rev Neurosci 7 1 54 64
54 - P. J Lang, 1995 The emotion probe: studies of motivation and attention. Am Psychol 50 372 385
55 - G Lázaro-Muñoz, J E LeDoux, C K Cain, 2010 Sidman instrumental avoidance initially depends on lateral and basal amygdala and is constrained by central amygdala-mediated Pavlovian processes Biol Psychiatry 67 1120 1127
56 - J E LeDoux, 2007 The amygdala. Curr Biol 17 868 874
57 - J E LeDoux, 2000 Emotion circuits in the brain. Annu Rev Neurosci 23 155 184
58 - P. M Lledo, G Gheusi, J. D Vincent, 2005 Information processing in the mammalian olfactory system. Physiol Rev 85 281 317
59 - S Maren, 1999 Neurotoxic basolateral amygdala lesions impair learning and memory but not the performance of conditional fear in rats. J Neurosci 19 8696 8703
60 - E Maron, D Nutt, J Shlik, 2012 Neuroimaging of serotonin system in anxiety disorders Curr Pharm Des in press.
61 - L Martínez-Mota, E Estrada-Camarena, C López-Rubalcava, C. M Contreras, A Fernández-Guasti, 2000 Interaction of desipramine with steroid hormones on experimental anxiety Psychoneuroendocrinology 25 109 120
62 - A. R Mawson, 2005 Understanding mass panic and other collective responses to threat and disaster. Psychiatry 68 2 95 113
63 - J Maynard-Smith, D Harper, 2003 Animal signals Oxford: Oxford University Press.
64 - M. E Medina-Mora, G Borges, C Lara, C Benjet, J Blanco, C Fleiz, J Villatoro, E Rojas, J Zambrano, L Casanova, S Aguilar-Gaxiola, 2003 Prevalencia de trastornos mentales y uso de servicios: resultados de la Encuesta Nacional de Epidemiología Psiquiátrica en México. Salud Mental 26 4 1 16
65 - J Menard, D Treit, 1999 Effects of centrally administered anxiolytic compounds in animal models of anxiety. Neurosci Biobehav Rev 23 4 591 613
66 - K Michelsson, K Christensson, H Rothgänger, J Winberg, 1996 Crying in separated and non-separated newborns: sound spectrographic analysis. Acta Paediatrica 85 4 471 475
67 - D. A Morilak, G Barrera, D. J Echevarria, A. S García, A Hernández, S Ma, C. O Petre, 2005 Role of brain norepinephrine in the behavioral response to stress Prog Neuropsychopharmacol Biol Psychiatry 29 8 1214 1224
68 - M Müller, M Fendt, 2006 Temporary inactivation of the medial and basolateral amygdala differentially affects TMT-induced fear behavior in rats Behav Brain Res 167 57 62
69 - K Nader, P Majidishad, P Amorapanth, J E LeDoux, 2001 Damage to the lateral and central, but not other, amygdaloid nuclei prevents the acquisition of auditory fear conditioning Learn Mem 8 156 163
70 - C. B Nemeroff, 2003a Anxiolytics past, present, and future agents. J Clin Psychiatry 64 3 6
71 - R Nowak, R. H Porter, F Lévy, P Orgeur, B Schaal, 2000 Role of mother-young interactions in the survival of offspring in domestic mammals. Rev Reprod 5 3 153 163
72 - D. J Nutt, A. L Malizia, 2001 New insights into the role of the GABAA-benzodiazepine receptor in psychiatric disorders. Br J Psychiatry 179 5 390 396
73 - L Pani, A Porcella, G. L Gessa, 2000 The role of stress in the pathophysiology of the dopaminergic system. Mol Psychiatry 5 1 14 21
74 - R. H Pastel, 2001 Collective behaviors: mass panic and outbreaks of multiple unexplained symptoms Mil Med 166 12 44 46
75 - P Pauli, C Marquardt, L Hartl, D. O Nutzinger, R Hölzl, F Strian, 1991 Anxiety induced by cardiac perceptions in patients with panic attacks: a field study. Behav Res Ther 29 2 137 145
76 - J. G Pelletier, E Likhtik, M Filali, D Paré, 2005 Lasting increases in basolateral amygdala activity after emotional arousal: implications for facilitated consolidation of emotional memories Learn Mem 12 96 102
77 - G. D Petrovich, N. S Canteras, L. W Swanson, 2001 Combinatorial amygdalar inputs to hippocampal domains and hypothalamic behavior systems. Brain Res Brain Res Rev 38 1-2 247 89
78 - G Piñeyro, P Blier, 1999 Autoregulation of serotonin neurons: role in antidepressant drug action. Pharmacol Rev 51 3 533 591
79 - S Pinker, R Jackendoff, 2005 The faculty of language: what’s special about it? Cognition 95 2 201 236
80 - R. H Porter, J Winberg, 1999 Unique salience of maternal breast odors for newborn infants. Neurosci Biobehav Rev 23 3 439 449
81 - F. E Regnier, 1971 Semiochemicals: structure and function. Biol Reprod 4 309 326
82 - L. M Romanski, J E LeDoux, 1992 Equipotentiality of thalamo-amygdala and thalamo-cortico-amygdala circuits in auditory fear conditioning. J Neurosci 12 11 4501 4509
83 - B Roozendaal, P Curt, 2000 Glucocorticoids and the regulation of memory consolidation. Psychoneuroendocrinology 25 213 238
84 - P Sah, E. S. L Faber, M Lopez de Armentia, J Power, 2003 The amygdaloid complex: anatomy and physiology. Physiol Rev 83 803 834
85 - B Schaal, 1988 Olfaction in infants and children: developmental and functional perspectives Chem Senses 13 2 145 190
86 - M Serra, M. G Pisu, M Littera, G Papi, E Sanna, F Tuveri, L Usala, R. H Purdy, G Biggio, 2000 Social isolation-induced decreases in both the abundance of neuroactive steroids and GABAA receptor function in rat brain. J Neurochem 75 2 732 740
87 - L. J Siever, R. S Kahn, B. A Lawlor, R. L Trestman, T. L Lawrence, E. F Coccaro, 1991 Critical issues in defining the role of serotonin in psychiatric disorders. Pharmacol Rev 43 4 509 525
88 - O. P Singh, N Mandal, A Biswas, S Mondal, S Sen, S Mukhopadhyay, 2009 An investigation into a mass psychogenic illness at Burdwan, West Bengal. Indian J Public Health 53 1 55 57
89 - W Sperling, S Bleich, U Reulbach, 2008 Black Monday on stock markets throughout the world: a new phenomenon of collective panic disorder? A psychiatric approach. Med Hypotheses 71 6 972 974
90 - L.G Staples, G.E Hunt, J.L Cornish, I.S McGregor, 2005 Neural activation during cat odor-induced conditioned fear and “trial 2” fear in rats. Neurosci Biobehav Rev 29 8 1265 1277
91 - S. C Stout, C. D Kilts, C. B Nemeroff, 1995 Neuropeptides and stress: preclinical findings and implication for pathophysiology. In: Friedman, M.J.; Charney, D.S. & Deutch, A.Y. (eds). Neurobiological and clinical consequences of stress: from normal adaptation to post-traumatic stress disorder 103 123 Philadelphia: Lippincott-Raven.
92 - L. W Swanson, G. D Petrovich, 1998 What is the amygdala? Trends Neurosci 21 8 323 331
93 - L. K Takahashi, D. T Hubbard, I Lee, Y Dar, S. M Sipes, 2007 Predator odor-induced conditioned fear involves the basolateral and medial amygdala. Behav Neurosci 121 100 110
94 - M. J Travis, T Bruce, 1994 Who cares for young carers? BMJ 309 6950 341
95 - N Tunçel, F. C Töre, 1998 The effect of vasoactive intestinal peptide (VIP) and inhibition of nitric oxide synthase on survival rate in rats exposed to endotoxin shock. Ann N Y Acad Sci 865 586 589
96 - M Uusi-oukari, E. R Korpi, 2010 Regulation of GABAA receptor subunit expression by pharmacological agents. Pharmacol Rev 62 1 97 135
97 - H Varendi, K Christensson, R. H Porter, J Winberg, 1998 Soothing effect of amniotic fluid smell in newborn infants. Early Hum Development 51 1 47 55
98 - H Varendi, R. H Porter, J Winberg, 1996 Attractiveness of amniotic fluid odor: evidence of prenatal learning? Acta Pediatrica 85 10 1223 1227
99 - E Vermetthen, J. D Bremner, 2002 Circuits and systems in stress: I. Preclinical studies. Depress Anxiety 15 126 147
100 - M. D Vermetten, D. S Charney, J. D Bremner, 2003 From anxiety disorders to PTSD.Vermetten, M.D. (ed). Posttraumatic stress disorder: neurobiological studies in the aftermath of traumatic stress 3 13 Utrecht: Remco Haringhuizen and Adriaan Kraal.
101 - G Villarreal, C. Y King, 2001 Brain imaging in posttraumatic stress disorder. Semin Clin Neuropsychiatry 6 131 145
102 - F Xu, M Schaefer, I Kida, J Schafer, N Liu, D. L Rothman, F Hyder, D Restrepo, G. M Shepherd, 2005 Simultaneous activation of mouse main and accessory olfactory bulbs by odors or pheromones. J Comp Neurol 489 491 500
103 - K Yamazaki, G. K Beauchamp, M Curran, J Bard, E. A Boyse, 2000 Parent-progeny recognition as a function of MHC odor type identity. Proc Natl Acad Sci U S A 97 10500 10502
104 - M. J Zigmond, S. L Castro, K. A Keefe, E. D Abercrombie, A. F Sved, 1998 Role of excitatory amino acids in the regulation of dopamine synthesis and release in the neostriatum. Amino Acids 57 62