Modulation of anxiety circuits by serotonergic systems

Anxiety is a complex emotional state associated with sustained heightened autonomic and behavioral arousal and an increase in avoidance behavior. Anxiety-related behavior is a form of risk assessment behavior that is associated with a level of uncertainty or unpredictability regarding the outcome of emotionally salient events, often when both rewarding and aversive outcomes are possible. In this review, we highlight recent advances in our understanding of the neural circuits regulating anxiety states and anxiety-related behavior with an emphasis on the role of brainstem serotonergic systems in modulating anxiety-related circuits. In particular, we explore the possibility that the regulation of anxiety states and anxiety-related behavior by serotonergic systems is dependent on a specific, topographically organized mesolimbocortical serotonergic system that originates in the mid-rostrocaudal and caudal parts of the dorsal raphe nucleus.

[1]  D. Paré,et al.  Infralimbic cortex activation increases c-fos expression in intercalated neurons of the amygdala , 2005, Neuroscience.

[2]  T. Sharp,et al.  Induction of c-Fos expression in specific areas of the fear circuitry in rat forebrain by anxiogenic drugs , 2003, Biological Psychiatry.

[3]  D. Nutt,et al.  Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders , 1999, European Neuropsychopharmacology.

[4]  J L McGaugh,et al.  Basolateral amygdala noradrenergic influence enables enhancement of memory consolidation induced by hippocampal glucocorticoid receptor activation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Adamec,et al.  Anxiolytic and anxiogenic effects of kindling—role of baseline anxiety and anatomical location of the kindling electrode in response to kindling of the right and left basolateral amygdala , 2005, Behavioural Brain Research.

[6]  S. Maier,et al.  Stressor controllability and learned helplessness: The roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor , 2005, Neuroscience & Biobehavioral Reviews.

[7]  J. Gray,et al.  The neuropsychology of anxiety: reprise. , 1996, Nebraska Symposium on Motivation. Nebraska Symposium on Motivation.

[8]  T. Robbins,et al.  Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala , 1997, Nature.

[9]  Eric R. Kandel,et al.  Identification of a Signaling Network in Lateral Nucleus of Amygdala Important for Inhibiting Memory Specifically Related to Learned Fear , 2002, Cell.

[10]  P. Dayan,et al.  Reward, Motivation, and Reinforcement Learning , 2002, Neuron.

[11]  A. Shekhar,et al.  Regulation of anxiety by GABAA receptors in the rat amygdala , 1995, Pharmacology Biochemistry and Behavior.

[12]  F P Valle,et al.  Effects of strain, sex, and illumination on open-field behavior of rats. , 1970, The American journal of psychology.

[13]  Stephen Maren,et al.  Pretraining NMDA receptor blockade in the basolateral complex, but not the central nucleus, of the amygdala prevents savings of conditional fear. , 2003, Behavioral neuroscience.

[14]  G. Hall,et al.  Preserved Sensitivity to Outcome Value after Lesions of the Basolateral Amygdala , 2003, The Journal of Neuroscience.

[15]  J. Gray.  A theory of anxiety: the role of the limbic system. , 1983, L'Encephale.

[16]  D. Murphy,et al.  Brain serotonin neurotransmission: an overview and update with an emphasis on serotonin subsystem heterogeneity, multiple receptors, interactions with other neurotransmitter systems, and consequent implications for understanding the actions of serotonergic drugs. , 1998, The Journal of clinical psychiatry.

[17]  S. File,et al.  5-HT1A and benzodiazepine receptors in the basolateral amygdala modulate anxiety in the social interaction test, but not in the elevated plus-maze , 1996, Brain Research.

[18]  J. Lisman,et al.  Hippocampus as comparator: Role of the two input and two output systems of the hippocampus in selection and registration of information , 2001, Hippocampus.

[19]  A. J. Bradbury,et al.  Behavioural and biochemical consequences following activation of 5HT1-like and GABA receptors in the dorsal raphé nucleus of the rat , 1988, Neuropharmacology.

[20]  Craig W. Berridge,et al.  Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses? , 1990, Brain Research Reviews.

[21]  R. Kahn,et al.  Serotonin and anxiety revisited , 1988, Biological Psychiatry.

[22]  D. Rainnie.  Serotonergic modulation of neurotransmission in the rat basolateral amygdala. , 1999, Journal of neurophysiology.

[23]  C. de Montigny,et al.  Benzodiazepine receptors modulate 5-hydroxytryptamine neurotransmission in the rat hippocampus: in vivo electrophysiological evidence. , 1990, The Journal of pharmacology and experimental therapeutics.

[24]  L. Heimer.  A new anatomical framework for neuropsychiatric disorders and drug abuse. , 2003, The American journal of psychiatry.

[25]  R. Valentino,et al.  A Neurochemically Distinct Dorsal Raphe-Limbic Circuit with a Potential Role in Affective Disorders , 2003, Neuropsychopharmacology.

[26]  C. Lowry,et al.  Urocortin 2 increases c-Fos expression in topographically organized subpopulations of serotonergic neurons in the rat dorsal raphe nucleus , 2005, Brain Research.

[27]  F. S. Hall,et al.  Differential basis of strain and rearing effects on open-field behavior in Fawn Hooded and Wistar rats , 2000, Physiology & Behavior.

[28]  A. Shekhar,et al.  Sodium lactate elicits anxiety in rats after repeated GABA receptor blockade in the basolateral amygdala. , 2000, European journal of pharmacology.

[29]  Michael Davis,et al.  Are different parts of the extended amygdala involved in fear versus anxiety? , 1998, Biological Psychiatry.

[30]  F. Graeff,et al.  Anxiolytic effect of intra-amygdala injection of midazolam and 8-hydroxy-2-(di-n-propylamino)tetralin in the elevated T-maze. , 1999, European journal of pharmacology.

[31]  J. D. McGaugh.  Memory consolidation and the amygdala: a systems perspective , 2002, Trends in Neurosciences.

[32]  M. Fendt,et al.  Temporary Inactivation of the Bed Nucleus of the Stria Terminalis But Not of the Amygdala Blocks Freezing Induced by Trimethylthiazoline, a Component of Fox Feces , 2003, The Journal of Neuroscience.

[33]  D. Treit,et al.  The central and basolateral amygdala differentially mediate the anxiolytic effects of benzodiazepines , 1995, Brain Research.

[34]  Eric R. Kandel,et al.  Individual Differences in Trait Anxiety Predict the Response of the Basolateral Amygdala to Unconsciously Processed Fearful Faces , 2004, Neuron.

[35]  K. Berridge.  Motivation concepts in behavioral neuroscience , 2004, Physiology & Behavior.

[36]  M. Walton,et al.  Action sets and decisions in the medial frontal cortex , 2004, Trends in Cognitive Sciences.

[37]  Michael Davis,et al.  Neurobiology of fear responses: the role of the amygdala. , 1997, The Journal of neuropsychiatry and clinical neurosciences.

[38]  Joseph E LeDoux,et al.  Activation of ERK/MAP Kinase in the Amygdala Is Required for Memory Consolidation of Pavlovian Fear Conditioning , 2000, The Journal of Neuroscience.

[39]  K. L. Gardner,et al.  Early life experience alters behavior during social defeat: Focus on serotonergic systems , 2005, Neuroscience.

[40]  C. Flachskamm,et al.  Effects of exposure to a predator on behaviour and serotonergic neurotransmission in different brain regions of C57bl/6N mice , 2005, The European journal of neuroscience.

[41]  J. Gray.  The neuropsychology of anxiety. , 1985, Issues in mental health nursing.

[42]  P. Shinnick‐Gallagher,et al.  A novel rat medial prefrontal cortical slice preparation to investigate synaptic transmission from amygdala to layer V prelimbic pyramidal neurons , 2006, Journal of Neuroscience Methods.

[43]  J. Feldon,et al.  Differential role of the medial and lateral prefrontal cortices in fear and anxiety. , 2000, Behavioral neuroscience.

[44]  C. Rampon,et al.  Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods , 1997, Neuroscience.

[45]  R. Rimondini,et al.  Local 5,7-Dihydroxytryptamine Lesions of Rat Amygdala: Release of Punished Drinking, Unaffected Plus-Maze Behavior and Ethanol Consumption , 2001, Neuropsychopharmacology.

[46]  M. Shapiro,et al.  Prospective and Retrospective Memory Coding in the Hippocampus , 2003, Neuron.

[47]  B. Olivier,et al.  The light-enhanced startle paradigm as a putative animal model for anxiety: effects of chlordiazepoxide, flesinoxan and fluvoxamine , 2002, Psychopharmacology.

[48]  V. Chan‐Palay,et al.  Immunohistochemical localization of serotonin nerve terminals in the lateral entorhinal cortex of the rat: Demonstration of two separate patterns of innervation from the midbrain raphe , 2004, Anatomy and Embryology.

[49]  E. Kandel,et al.  Control of Memory Formation Through Regulated Expression of a CaMKII Transgene , 1996, Science.

[50]  K. Berridge,et al.  What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? , 1998, Brain Research Reviews.

[51]  K. Jeffery.  Remembrance of futures past , 2004, Trends in Cognitive Sciences.

[52]  D. Nutt.  Neurobiological mechanisms in generalized anxiety disorder. , 2001, The Journal of clinical psychiatry.

[53]  M. Hajós,et al.  An electrophysiological and neuroanatomical study of the medial prefrontal cortical projection to the midbrain raphe nuclei in the rat , 1998, Neuroscience.

[54]  S. Campeau,et al.  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 , 2004, Brain Research.

[55]  A. Shekhar,et al.  Role of corticotropin-releasing factor and urocortin within the basolateral amygdala of rats in anxiety and panic responses , 1999, Behavioural Brain Research.

[56]  Joseph E LeDoux,et al.  The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[57]  S. Maier,et al.  Microinjection of urocortin 2 into the dorsal raphe nucleus activates serotonergic neurons and increases extracellular serotonin in the basolateral amygdala , 2004, Neuroscience.

[58]  P. Morgane,et al.  A review of systems and networks of the limbic forebrain/limbic midbrain , 2005, Progress in Neurobiology.

[59]  D. Nutt.  Overview of Diagnosis and Drug Treatments of Anxiety Disorders , 2005, CNS Spectrums.

[60]  D. Blanchard,et al.  Attack and defense in rodents as ethoexperimental models for the study of emotion , 1989, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[61]  M. Davis,et al.  5-hydroxytryptamine1A-like receptor activation in the bed nucleus of the stria terminalis: electrophysiological and behavioral studies. , 2004, Neuroscience.

[62]  D. van der Kooy,et al.  The nucleus raphe dorsalis of the rat and its projection upon the caudatoputamen. A combined cytoarchitectonic, immunohistochemical and retrograde transport study. , 1981, Journal de physiologie.

[63]  Michael Davis,et al.  Light-enhanced startle: further pharmacological and behavioral characterization , 2001, Psychopharmacology.

[64]  F. Graeff,et al.  Serotonergic regulation of inhibitory avoidance and one-way escape in the rat elevated T-maze , 2001, Neuroscience & Biobehavioral Reviews.

[65]  G. Higgins,et al.  Effect of 5-HT1A receptor agonists in two models of anxiety after dorsal raphe injection , 2007, Psychopharmacology.

[66]  G. Dockray,et al.  Measurement of secretory vesicle pH reveals intravesicular alkalinization by vesicular monoamine transporter type 2 resulting in inhibition of prohormone cleavage , 2001, The Journal of physiology.

[67]  T. Hattori,et al.  Dorsal raphe cells with collateral projections to the caudate-putamen and substantia nigra: A fluorescent retrograde double labeling study in the rat , 1980, Brain Research.

[68]  S. Maier,et al.  The dorsal raphe nucleus is a site of action mediating the behavioral effects of the benzodiazepine receptor inverse agonist DMCM. , 1995, Behavioral neuroscience.

[69]  O. Ottersen.  Afferent connections to the amygdaloid complex of the rat with some observations in the cat. III. Afferents from the lower brain stem , 1981, The Journal of comparative neurology.

[70]  George R. Breese,et al.  Neuroanatomical characterization of Fos induction in rat behavioral models of anxiety , 1996, Brain Research.

[71]  S. Maier,et al.  Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus , 2005, Nature Neuroscience.

[72]  R. Martinez,et al.  SHORT COMMUNICATIONS: Increases in extracellular levels of 5‐HT and dopamine in the basolateral, but not in the central, nucleus of amygdala induced by aversive stimulation of the inferior colliculus , 2005, The European journal of neuroscience.

[73]  T. Petrov,et al.  Chemically defined collateral projections from the pons to the central nucleus of the amygdala and hypothalamic paraventricular nucleus in the rat , 1994, Cell and Tissue Research.

[74]  T. Curran,et al.  Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. , 1991, Annual review of neuroscience.

[75]  F. Graeff,et al.  The elevated T-maze as an experimental model of anxiety , 1998, Neuroscience & Biobehavioral Reviews.

[76]  J L McGaugh,et al.  Basolateral amygdala noradrenergic influences on memory storage are mediated by an interaction between beta- and alpha1-adrenoceptors. , 1999, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[77]  G. Griebel.  5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders: more than 30 years of research. , 1995, Pharmacology & therapeutics.

[78]  James L. McGaugh,et al.  Basolateral Amygdala Noradrenergic Influences on Memory Storage Are Mediated by an Interaction between β- and α1-Adrenoceptors , 1999, The Journal of Neuroscience.

[79]  M. Davis,et al.  5-hydroxytryptamine1a-likereceptor activation in the bed nucleus of the stria terminalis: Electrophysiological and behavioral studies , 2004, Neuroscience.

[80]  J. D. McGaugh,et al.  Post-Training Intra-Basolateral Amygdala Infusions of Norepinephrine Enhance Consolidation of Memory for Contextual Fear Conditioning , 2003, The Journal of Neuroscience.

[81]  Michael Davis,et al.  Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala , 1990, Nature.

[82]  Michael Davis,et al.  Lesions of the bed nucleus of the stria terminalis block sensitization of the acoustic startle reflex produced by repeated stress, but not fear-potentiated startle , 1998, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[83]  D. Nutt,et al.  Brain mechanisms of social anxiety disorder. , 1998, The Journal of clinical psychiatry.

[84]  O. Kretz,et al.  Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety , 1999, Nature Genetics.

[85]  A. Kelley.  Memory and Addiction Shared Neural Circuitry and Molecular Mechanisms , 2004, Neuron.

[86]  A. Shekhar,et al.  Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs , 2005, Neuroscience.

[87]  Joseph E LeDoux,et al.  Serotonin Modulation of Sensory Inputs to the Lateral Amygdala: Dependency on Corticosterone , 1998, The Journal of Neuroscience.

[88]  R. A. Fuchs,et al.  Potentiated Reinstatement of Cocaine-Seeking Behavior Following D-amphetamine Infusion into the Basolateral Amygdala , 2003, Neuropsychopharmacology.

[89]  T. Kaneko,et al.  Collateral projections of nucleus raphe dorsalis neurones to the caudate-putamen and region around the nucleus raphe magnus and nucleus reticularis gigantocellularis pars α in the rat , 2001, Neuroscience Letters.

[90]  L Stein,et al.  Benzodiazepines: Anxiety-Reducing Activity by Reduction of Serotonin Turnover in the Brain , 1972, Science.

[91]  S. Iversen.  5-HT and anxiety , 1984, Neuropharmacology.

[92]  C. A. Lowry,et al.  Functional Subsets of Serotonergic Neurones: Implications for Control of the Hypothalamic‐Pituitary‐Adrenal Axis , 2002, Journal of neuroendocrinology.

[93]  M. Patil,et al.  Behavioral / Systems / Cognitive Corticotrophin Releasing Factor-Induced Synaptic Plasticity in the Amygdala Translates Stress into Emotional Disorders , 2004 .

[94]  F. Graeff,et al.  Role of 5-HT in stress, anxiety, and depression , 1996, Pharmacology Biochemistry and Behavior.

[95]  R. See,et al.  Lesions of the basolateral amygdala abolish the ability of drug associated cues to reinstate responding during withdrawal from self-administered cocaine , 1997, Behavioural Brain Research.

[96]  S. Handley.  5-Hydroxytryptamine pathways in anxiety and its treatment. , 1995, Pharmacology & therapeutics.

[97]  E. V. Bockstaele,et al.  Topography of serotonin neurons in the dorsal raphe nucleus that send axon collaterals to the rat prefrontal cortex and nucleus accumbens , 1993, Brain Research.

[98]  G. Koob,et al.  Corticotropin-releasing factor and neuropeptide y: role in emotional integration , 1994, Trends in Neurosciences.

[99]  Kovács Kj.  c-Fos as a transcription factor : a stressful (re)view from a functional map , 1998 .

[100]  S. T. Kitai,et al.  The organization of divergent axonal projections from the midbrain raphe nuclei in the rat , 1986, The Journal of comparative neurology.

[101]  J. Masur,et al.  Evaluation of psychotropic drugs with a modified open field test. , 1978, Pharmacology.

[102]  F. Graeff,et al.  Dual role of 5-HT in defense and anxiety , 1997, Neuroscience & Biobehavioral Reviews.

[103]  K. Kovács,et al.  Invited review c-Fos as a transcription factor: a stressful (re)view from a functional map , 1998, Neurochemistry International.

[104]  T. Phan,et al.  Further studies on the activation of rat median raphe serotonergic neurons by inescapable sound stress , 2001, Brain Research.

[105]  Younglim Lee,et al.  Effect of corticosterone on the enhancement of the acoustic startle reflex by corticotropin releasing factor (CRF) , 1994, Brain Research.

[106]  T. Sharp,et al.  Neuroanatomical targets of anxiogenic drugs in the hindbrain as revealed by Fos immunocytochemistry , 2000, Neuroscience.

[107]  T. Insel,et al.  Limits to growth: why neuroscience needs large-scale science , 2004, Nature Neuroscience.

[108]  K. Merchant,et al.  Serotonin 2C receptors within the basolateral amygdala induce acute fear-like responses in an open-field environment , 2003, Brain Research.

[109]  A. Shekhar,et al.  Interactions between NPY and CRF in the amygdala to regulate emotionality , 2004, Neuropeptides.

[110]  T. Petrov,et al.  The hypothalamic paraventricular and lateral parabrachial nuclei receive collaterals from raphe nucleus neurons: A combined double retrograde and immunocytochemical study , 1992, The Journal of comparative neurology.

[111]  H. Steinbusch,et al.  Identification of serotonin and non-serotonin-containing neurons of the mid-brain raphe projecting to the entorhinal area and the hippocampal formation. A combined immunohistochemical and fluorescent retrograde tracing study in the rat brain , 1982, Neuroscience.

[112]  R. Schreiber,et al.  Neuronal circuits involved in the anxiolytic effects of the 5-HT1A receptor agonists 8-OH-DPAT ipsapirone and buspirone in the rat. , 1993, European journal of pharmacology.

[113]  J. D. McGaugh,et al.  Involvement of stress-released corticotropin-releasing hormone in the basolateral amygdala in regulating memory consolidation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[114]  S. Maier,et al.  Stressor Controllability, Anxiety, and Serotonin , 1998, Cognitive Therapy and Research.

[115]  H. Steinbusch,et al.  The distribution and origin of serotonin‐containing fibers in the septal area: A combined immunohistochemical and fluorescent retrograde tracing study in the rat , 1982, The Journal of comparative neurology.

[116]  M. Davis,et al.  Involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[117]  B. Jacobs,et al.  A subgroup of dorsal raphe serotonergic neurons in the cat is strongly activated during oral-buccal movements , 1996, Brain Research.

[118]  S. Maier,et al.  Corticotropin Releasing Hormone Type 2 Receptors in the Dorsal Raphe Nucleus Mediate the Behavioral Consequences of Uncontrollable Stress , 2003, The Journal of Neuroscience.

[119]  S. Crochet,et al.  Differentiation of presumed serotonergic dorsal raphe neurons in relation to behavior and wake–sleep states , 2001, Neuroscience.

[120]  G. Holstege.  The Basic, Somatic, And Emotional Components Of The Motor System In Mammals. , 1995 .

[121]  R. Hen,et al.  Altered Emotional States in Knockout Mice Lacking 5-HT1A or 5-HT1B Receptors , 1999, Neuropsychopharmacology.

[122]  J. D. McGaugh,et al.  Basolateral Amygdala–Nucleus Accumbens Interactions in Mediating Glucocorticoid Enhancement of Memory Consolidation , 2001, The Journal of Neuroscience.

[123]  G. Aghajanian,et al.  Inhibition of neurons in the amygdala by dorsal raphe stimulation: Mediation through a direct serotonergic pathway , 1977, Brain Research.

[124]  Joseph E LeDoux,et al.  Fear conditioning induces associative long-term potentiation in the amygdala , 1997, Nature.

[125]  M. Millan,et al.  The neurobiology and control of anxious states , 2003, Progress in Neurobiology.

[126]  B. Jacobs,et al.  Activity of serotonin-containing neurons in nucleus centralis superior of freely moving cats , 1984, Experimental Neurology.

[127]  D. Albrecht,et al.  5‐HT1A receptor‐mediated inhibition and 5‐HT2 as well as 5‐HT3 receptor‐mediated excitation in different subdivisions of the rat amygdala , 2000, Synapse.

[128]  T. Gray,et al.  The amygdala: corticotropin-releasing factor, steroids, and stress. , 1996, Critical reviews in neurobiology.

[129]  L. Hernández,et al.  Tonic and phasic alteration in amygdala 5-HT, glutamate and GABA transmission after prefrontal cortex damage in rats , 2004, Brain Research.

[130]  R. Roesler,et al.  Differential involvement of hippocampal and amygdalar NMDA receptors in contextual and aversive aspects of inhibitory avoidance memory in rats , 2003, Brain Research.

[131]  J. Gray,et al.  Précis of The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system , 1982, Behavioral and Brain Sciences.

[132]  David J Nuit,et al.  The neurochemistry of anxiety: An update , 1990, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[133]  C. Hough,et al.  Serotonin type II receptor activation facilitates synaptic plasticity via n-methyl-d-aspartate-mediated mechanism in the rat basolateral amygdala , 2003, Neuroscience.

[134]  D. Nutt,et al.  Serotonin and panic , 1998, British Journal of Psychiatry.

[135]  Mitsuo Nakamura,et al.  Neural systems for behavioral activation and reward , 1999, Current Opinion in Neurobiology.

[136]  Hong-wei Dong,et al.  Topography of projections from amygdala to bed nuclei of the stria terminalis , 2001, Brain Research Reviews.

[137]  F. Graeff.  On serotonin and experimental anxiety , 2002, Psychopharmacology.

[138]  A. Meyer-Lindenberg,et al.  5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression , 2005, Nature Neuroscience.

[139]  M. Jackson,et al.  Stimulus‐specific plasticity of prefrontal cortex dopamine neurotransmission , 2004, Journal of neurochemistry.

[140]  Michael Davis,et al.  Anxiogenic effects of high illumination levels assessed with the acoustic startle response in rats , 1997, Biological Psychiatry.

[141]  Michael Davis,et al.  Role of the bed nucleus of the stria terminalis versus the amygdala in fear, stress, and anxiety. , 2003, European journal of pharmacology.