Dopaminergic Innervation of the Amygdala Is Highly Responsive to Stress

Abstract : The amygdala has been implicated in the neuronal sequelae of stress, although little is known about the neurochemical mechanisms underlying amygdala transmission. In vivo microdialysis was employed to measure extracellular levels of dopamine in the basolateral nucleus of the amygdala in awake rats. Once it was established that impulse‐dependent release of dopamine could be measured reliably in the amygdala, the effect of stress, induced by mild handling, on amygdala dopamine release was compared with that in three other dopamine‐innervated regions, the medial prefrontal cortex, nucleus accumbens, and caudate nucleus. The magnitude of increase in dopamine in response to the handling stimulus was significantly greater in the amygdala than in the nucleus accumbens and prefrontal cortex. This increase was maximal during the application of stress and diminished after the cessation of stress. In contrast, the increases in extracellular dopamine levels in other regions, in particular the nucleus accumbens, were prolonged, reaching maximal values after the cessation of stress. These results suggest that dopaminergic innervation of the amygdala may be more responsive to stress than that of other dopamine‐innervated regions of the limbic system, including the prefrontal cortex, and implicate amygdalar dopamine in normal and pathophysiological processes subserving an organism's response to stress.

[1]  J. Fallon,et al.  Catecholamine innervation of the basal forebrain II. Amygdala, suprarhinal cortex and entorhinal cortex , 1978, The Journal of comparative neurology.

[2]  The Neurobiology of Drug Addiction , 1997 .

[3]  A. Hajnal,et al.  Feeding‐related dopamine in the amygdala of freely moving rats , 1997, Neuroreport.

[4]  G. Mogenson,et al.  Mesolimbic dopamine projection modulates amygdala-evoked EPSP in nucleus accumbens neurons: an in vivo study , 1986, Brain Research.

[5]  B. Westerink,et al.  The role of afferents to the ventral tegmental area in the handling stress-induced increase in the release of dopamine in the medial prefrontal cortex: a dual-probe microdialysis study in the rat brain , 1998, Brain Research.

[6]  M. Mesulam,et al.  Two types of cholinergic projections to the rat amygdala , 1994, Neuroscience.

[7]  B. Moghaddam,et al.  The Prefrontal Cortex Regulates the Basal Release of Dopamine in the Limbic Striatum: An Effect Mediated by Ventral Tegmental Area , 1996, Journal of neurochemistry.

[8]  M. Savasta,et al.  Autoradiographic distribution of the D1 agonist [3H]SKF 38393, in the rat brain and spinal cord. Comparison with the distribution of D2 dopamine receptors , 1986, Neuroscience.

[9]  B. Moghaddam,et al.  Glutamatergic Control of Dopamine Release During Stress in the Rat Prefrontal Cortex , 1994, Journal of neurochemistry.

[10]  Y. Shaham,et al.  Relapse to heroin-seeking in rats under opioid maintenance: the effects of stress, heroin priming, and withdrawal , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  O. Ottersen,et al.  Connections of the amygdala of the rat. IV: Corticoamygdaloid and intraamygdaloid connections as studied with axonal transport of horseradish peroxidase , 1982, The Journal of comparative neurology.

[12]  A. Malla,et al.  Stressful Life Events and Schizophrenia II: Conceptual and Methodological Issues , 1993, British Journal of Psychiatry.

[13]  J. Fallon,et al.  Catecholamine innervation of the basal forebrain IV. Topography of the dopamine projection to the basal forebrain and neostriatum , 1978, The Journal of comparative neurology.

[14]  T. Dawson,et al.  D-1 dopamine receptors in the rat brain: a quantitative autoradiographic analysis , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  Masatoshi Tanaka,et al.  Noradrenaline release in the rat amygdala is increased by stress: studies with intracerebral microdialysis , 1991, Brain Research.

[16]  O. Shirakawa,et al.  Isotype-Specific G Protein Abnormalities in the Left Superior Temporal Cortex and Limbic Structures of Patients with Chronic Schizophrenia , 1998, Biological Psychiatry.

[17]  Joseph E LeDoux.  Brain mechanisms of emotion and emotional learning , 1992, Current Opinion in Neurobiology.

[18]  H. Kita,et al.  Amygdaloid projections to the frontal cortex and the striatum in the rat , 1990, The Journal of comparative neurology.

[19]  E. Abercrombie,et al.  Differential Effect of Stress on In Vivo Dopamine Release in Striatum, Nucleus Accumbens, and Medial Frontal Cortex , 1989, Journal of neurochemistry.

[20]  M. Davis,et al.  N-methyl-D-aspartate lesions of the lateral and basolateral nuclei of the amygdala block fear-potentiated startle and shock sensitization of startle. , 1992, Behavioral neuroscience.

[21]  A. Ohman,et al.  Relationships between social support, social coping and life events in the relapse of schizophrenic patients. , 1997, Scandinavian journal of psychology.

[22]  G. Buzsáki,et al.  Nucleus basalis and thalamic control of neocortical activity in the freely moving rat , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  H. Klüver,et al.  PRELIMINARY ANALYSIS OF FUNCTIONS OF THE TEMPORAL LOBES IN MONKEYS , 1939 .

[24]  Peter W. Kalivas,et al.  Selective activation of dopamine transmission in the shell of the nucleus accumbens by stress , 1995, Brain Research.

[25]  S. Hyman,et al.  Acute Effects of Cocaine on Human Brain Activity and Emotion , 1997, Neuron.

[26]  A. Dunn.  Stress‐Related Activation of Cerebral Dopaminergic Systems a , 1988, Annals of the New York Academy of Sciences.

[27]  L. Heimer,et al.  Ultrastructural evidence of amygdalofugal axons terminating on cholinergic cells of the rostral forebrain , 1984, Neuroscience Letters.

[28]  M. Davis,et al.  Enhancement of acoustic startle by electrical stimulation of the amygdala. , 1988, Behavioral neuroscience.

[29]  M Mishkin,et al.  Amygdalectomy impairs crossmodal association in monkeys. , 1985, Science.

[30]  T. Robbins,et al.  Involvement of the amygdala in stimulus-reward associations: Interaction with the ventral striatum , 1989, Neuroscience.

[31]  Masatoshi Tanaka,et al.  Psychological stress increases serotonin release in the rat amygdala and prefrontal cortex assessed by in vivo microdialysis , 1993, Neuroscience Letters.

[32]  W. Nauta,et al.  The amygdalostriatal projection in the rat—an anatomical study by anterograde and retrograde tracing methods , 1982, Neuroscience.

[33]  J. Price,et al.  Amygdaloid projections to subcortical structures within the basal forebrain and brainstem in the rat and cat , 1978, The Journal of comparative neurology.

[34]  C. Y. Yim,et al.  Response of nucleus accumbens neurons to amygdala stimulation and its modification by dopamine , 1982, Brain Research.

[35]  J. Price,et al.  Projections from the amygdaloid complex to the cerebral cortex and thalamus in the rat and cat , 1977, The Journal of comparative neurology.

[36]  J. Saavedra,et al.  Tyrosine hydroxylase and dopamine-β-hydroxylase: distribution in discrete areas of the rat limbic system , 1976, Brain Research.

[37]  J. Tanaka,et al.  Effects of discrimination learning on the rat amygdala dopamine release: a microdialysis study , 1993, Brain Research.

[38]  M. Zigmond,et al.  Effects of dopamine depletion in the medial prefrontal cortex on the stress-induced increase in extracellular dopamine in the nucleus accumbens core and shell , 1997, Neuroscience.

[39]  A. Imperato,et al.  Stress activation of limbic and cortical dopamine release is prevented by ICS 205-930 but not by diazepam. , 1990, European journal of pharmacology.

[40]  P. Piazza,et al.  Social stress increases the acquisition of cocaine self-administration in male and female rats , 1995, Brain Research.

[41]  A. Imperato,et al.  Changes in brain dopamine and acetylcholine release during and following stress are independent of the pituitary-adrenocortical axis , 1991, Brain Research.

[42]  C. Kilts,et al.  Mesoamygdaloid dopamine neurons: differential rates of dopamine turnover in discrete amygdaloid nuclei of the rat brain , 1987, Brain Research.

[43]  P. Garris,et al.  Different kinetics govern dopaminergic transmission in the amygdala, prefrontal cortex, and striatum: an in vivo voltammetric study , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[44]  J. Glowinski,et al.  Selective activation of the mesocortical DA system by stress , 1976, Nature.

[45]  S. Haber,et al.  The interface between dopamine neurons and the amygdala: implications for schizophrenia. , 1997, Schizophrenia bulletin.

[46]  W. Nauta,et al.  Efferent connections of the substantia nigra and ventral tegmental area in the rat , 1979, Brain Research.

[47]  M. Palkovits,et al.  Effects of single or repeated immobilization on release of norepinephrine and its metabolites in the central nucleus of the amygdala in conscious rats. , 1993, Neuroendocrinology.

[48]  G. Koob,et al.  The neurobiology of drug addiction. , 1997, The Journal of neuropsychiatry and clinical neurosciences.

[49]  R. Roth,et al.  Stress and the Mesocorticolimbic Dopamine Systems a , 1988, Annals of the New York Academy of Sciences.

[50]  M. Feenstra,et al.  Local Activation of Metabotropic Glutamate Receptors Inhibits the Handling‐Induced Increased Release of Dopamine in the Nucleus Accumbens but Not that of Dopamine or Noradrenaline in the Prefrontal Cortex: Comparison with Inhibition of Ionotropic Receptors , 1998, Journal of neurochemistry.

[51]  G Oakson,et al.  Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[52]  L. Swanson.  The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[53]  Craig W. Berridge,et al.  Stress-induced activation of prefrontal cortex dopamine turnover: blockade by lesions of the amygdala , 1994, Brain Research.

[54]  U. Ungerstedt.  Stereotaxic mapping of the monoamine pathways in the rat brain. , 1971, Acta physiologica Scandinavica. Supplementum.

[55]  M. Wolf,et al.  Effects of lesions of prefrontal cortex, amygdala, or fornix on behavioral sensitization to amphetamine: Comparison with N-methyl-d-aspartate antagonists , 1995, Neuroscience.

[56]  G. Phillips,et al.  Repeated d-amphetamine enhances stimulated mesoamygdaloid dopamine transmission , 1997, Psychopharmacology.

[57]  G. Biggio,et al.  Modulation of basal and stress-induced release of acetylcholine and dopamine in rat brain by abecarnil and imidazenil, two anxioselective gamma-aminobutyric acidA receptor modulators. , 1995, The Journal of pharmacology and experimental therapeutics.

[58]  M. Feenstra,et al.  Rapid sampling of extracellular dopamine in the rat prefrontal cortex during food consumption, handling and exposure to novelty , 1996, Brain Research.

[59]  J. Price,et al.  Projections from the amygdaloid complex and adjacent olfactory structures to the entorhinal cortex and to the subiculum in the rat and cat , 1977, The Journal of comparative neurology.

[60]  H. Fibiger,et al.  Enhanced acetylcholine release in hippocampus and cortex during the anticipation and consumption of a palatable meal , 1994, Neuroscience.

[61]  G. Biggio,et al.  Inhibition of basal and stress-induced dopamine release in the cerebral cortex and nucleus accumbens of freely moving rats by the neurosteroid allopregnanolone , 1996, Journal of psychopharmacology.

[62]  S. Totterdell,et al.  Input from the amygdala to the rat nucleus accumbens: Its relationship with tyrosine hydroxylase immunoreactivity and identified neurons , 1994, Neuroscience.

[63]  Michael Davis,et al.  The role of the amygdala in conditioned fear. , 1992 .

[64]  R. Wise,et al.  Increase of Extracellular Glutamate and Expression of Fos‐Like Immunoreactivity in the Ventral Tegmental Area in Response to Electrical Stimulation of the Prefrontal Cortex , 1998, Journal of neurochemistry.

[65]  Michael Davis,et al.  Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm. , 1986, Behavioral neuroscience.

[66]  R. Roth,et al.  Role of the Amygdala in the Coordination of Behavioral, Neuroendocrine, and Prefrontal Cortical Monoamine Responses to Psychological Stress in the Rat , 1996 .

[67]  B. Moghaddam,et al.  Glutamatergic Regulation of Basal and Stimulus‐Activated Dopamine Release in the Prefrontal Cortex , 1998, Journal of neurochemistry.

[68]  G. Phillips,et al.  Enhanced acquisition of discriminative approach following intra-amygdala d-amphetamine , 1997, Psychopharmacology.

[69]  R. M. Beckstead.  An autoradiographic examination of corticocortical and subcortical projections of the mediodorsal‐projection (prefrontal) cortex in the rat , 1979, The Journal of comparative neurology.

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

[71]  C. Kilts,et al.  Selective activation of mesoamygdaloid dopamine neurons by conditioned stress: attenuation by diazepam , 1992, Brain Research.

[72]  H. Fibiger,et al.  Increases in hippocampal and frontal cortical acetylcholine release associated with presentation of sensory stimuli , 1995, Neuroscience.

[73]  D. Gaffan,et al.  Amygdalectomy and disconnection in visual learning for auditory secondary reinforcement by monkeys , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.