Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

The role of stress in the pathophysiology of the dopaminergic system

Abstract

In this review, we will examine the most recent preclinical evidence in support of the fact that both acute and chronic stress may have a detrimental impact on the normal function of the dopaminergic system. In recent decades, the term stress has changed its meaning from that of a ‘non-specific body response’ to a ‘monitoring system of internal and external cues’; that is a modality of reaction of the mammalian central nervous system (CNS) which is critical to the adaptation of the organism to its environment. Compelling results have demonstrated that the dopaminergic system is important not only for hedonic impact or reward learning but also, in a broader sense, for reactivity to perturbation in environmental conditions, for selective information processing, and for general emotional responses, which are essential functions in the ability (or failure) to cope with the external world. In this, stress directly influences several basic behaviors which are mediated by the dopaminergic system such as locomotor activity, sexual activity, appetite, and cross sensitization with drugs of abuse. Studies using rat lines which are genetically different in dopamine (DA) physiology, have shown that even small alterations in the birth procedure or early life stress events may contribute to the pathophysiology of psychiatric disorders—in particular those involving central DA dysfunction—and may cause depression or psychotic derangement in the offspring. Finally, the fact that the dopaminergic system after stress responds, preferentially, in the medial prefrontal cortex (MFC), is thought to serve, in humans, as a protection against positive psychotic symptoms, since the increased DA activity in the MFC suppresses limbic DA transmission. However, excessive MFC dopaminergic activity has a negative impact on the cognitive functions of primates, making them unable to select and process significant environmental stimuli. Thus it appears that a critical range of DA turnover is necessary for optimal cognitive functioning after stress, in the response of the CNS to ever-changing environmental demands.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Selye H . The evolution of the stress concept Am Sci 1973; 61: 692–696

    CAS  PubMed  Google Scholar 

  2. Akil HA, Morano IM . Stress. In: Kupfer D, Bloom F (eds) Psychopharmacology, the Fourth Generation of Progress Raven Press: New York 1995; pp773–785

    Google Scholar 

  3. Pani L, Gessa GL . Evolution of the dopaminergic system and its relationships with the psychopathology of pleasure Int J Clin Pharm Res 1997; 17: 55–58

    CAS  Google Scholar 

  4. Berridge KC, Robinson TE . What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Rev 1998; 28: 309–369

    Article  CAS  PubMed  Google Scholar 

  5. Wise RA . The brain and reward. In: Liebman J, Cooper SJ (eds) The Neuropharmacological Basis of Reward Oxford University Press: Oxford 1989; pp377–424

    Google Scholar 

  6. Fibiger HC, Phillips AG . Role of catecholamine transmitters in reward systems: implications for the neurobiology of affect. In: Oreland E (ed) Brain Reward Systems and Abuse New York Press: New York 1987; pp61–74

    Google Scholar 

  7. Blackburn JR, Pfaus JG, Phillips AG . Dopamine functions in appetitive and defensive behaviors Progr Neurobiol 1992; 39: 247–279

    Article  CAS  Google Scholar 

  8. Kaneyuki H, Yokoo H, Tsuda A, Yoshida M, Mizuki Y, Yamada M et al. Psychological stress increases dopamine turnover selectively in mesoprefrontal dopamine neurons of rats: reversal by diazepam Brain Res 1991; 557: 154–161

    Article  CAS  PubMed  Google Scholar 

  9. Doherty MD, Gratton A . NMDA receptors in nucleus accumbens modulate stress-induced dopamine release in nucleus accumbens and ventral tegmental area Synapse 1997; 26: 225–234

    Article  CAS  PubMed  Google Scholar 

  10. King D, Zigmond MJ, Finlay JM . Effects of dopamine depletion in the medial prefrontal cortex on the stress-induced increase in extracellular dopamine in the nucleus accumbens core and shell Neuroscience 1997; 77: 141–153

    Article  CAS  PubMed  Google Scholar 

  11. King D, Finlay JM . Loss of dopamine terminals in the medial prefrontal cortex increased the ratio of DOPAC to DA in tissue of the nucleus accumbens shell: role of stress Brain Res 1997; 767: 192–200

    Article  CAS  PubMed  Google Scholar 

  12. Griffiths J, Shanks N, Anisman H . Strain-specific alterations in consumption of a palatable diet following repeated stressor exposure Pharmacol Biochem Behav 1992; 42: 219–227

    Article  CAS  PubMed  Google Scholar 

  13. Sato Y, Kumamoto Y . Psychological stress and sexual behavior in male rats. II. Effect of psychological stress on dopamine and its metabolites in the critical brain areas mediating sexual behavior Nippon Hinyokika Gakkai Zasshi 1992; 83: 212–219

    CAS  PubMed  Google Scholar 

  14. Wang CT, Huang RL, Tai MY, Tsai YF, Peng MT . Dopamine release in the nucleus accumbens during sexual behavior in prenatally stressed adult male rats Neurosci Lett 1995; 200: 29–32

    Article  CAS  PubMed  Google Scholar 

  15. Sugiura K, Yoshimura H, Yokoyama M . An animal model of copulatory disorder induced by social stress in male mice: effects of apomorphine and L. dopa Psychopharmacol Berl 1997; 133: 249–255

    Article  CAS  Google Scholar 

  16. Brake WG, Noel MB, Boksa P, Gratton A . Influence of perinatal factors on the nucleus accumbens dopamine response to repeated stress during adulthood: an electrochemical study in the rat Neuroscience 1997; 77: 1067–1076

    Article  CAS  PubMed  Google Scholar 

  17. Alonso SJ, Navarro E, Rodriguez M . Permanent dopaminergic alterations in the n. accumbens after prenatal stress Pharmacol Biochem Behav 1994; 49: 353–358

    Article  CAS  PubMed  Google Scholar 

  18. Zebrowska-Lupina I, Stelmasiak M, Porowska A . Stress, induced depression of basal motility: effects of antidepressant drugs Pol J Pharmacol Pharm 1990; 42: 97–104

    CAS  PubMed  Google Scholar 

  19. Sampson D, Willner P, Muscat R . Reversal of antidepressant action by dopamine antagonists in an animal model of depression Psychopharmacol Berl 1991; 104: 491–495

    Article  CAS  Google Scholar 

  20. Zebrowscka-Lupina I, Ossowska G, Klenk-Majewska B . The influence of antidepressants on aggressive behavior in stressed rats: the role of dopamine Pol J Pharmacol Pharm 1992; 44: 325–335

    Google Scholar 

  21. Sampson D, Willner P, Muscat R . Reversal of antidepressant action by dopamine antagonists in an animal model of depression Psychopharmacol Berl 1991; 104: 491–495

    Article  CAS  Google Scholar 

  22. Muscat R, Papp M, Willner P . Reversal of stress, induced anhedonia by the atypical antidepressants, fluoxetine and maprotiline Psychopharmacol Berl 1992; 109: 433–438

    Article  CAS  Google Scholar 

  23. Papp M, Willner P, Muscat R . Behavioural sensitization to a dopamine agonist is associated with reversal of stress, induced anhedonia Psychopharmacol Berl 1993; 110: 159–164

    Article  CAS  Google Scholar 

  24. Papp M, Muscat R, Willner P . Subsensitivity to rewarding and locomotor stimulant effects of a dopamine agonist following chronic mild stress Psychopharmacol Berl 1993; 110: 152–158

    Article  CAS  Google Scholar 

  25. Willner P . Pharmacology of anhedonia Eur Neuropsychopharmacol 1995; 5: (suppl 3) 214s–221s

    Article  Google Scholar 

  26. Murphy BL, Arnsten AF, Goldman-Rakic PS, Roth RH . Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys Proc Natl Acad Sci USA 1996; 93: 1325–1329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Murphy BL, Arnsten AF, Jentsch JD, Roth RH . Dopamine and spatial working memory in rats and monkeys: pharmacological reversal of stress, induced impairment J Neurosci 1996; 16: 7768–7775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Steketee JD, Kalivas PW . Sensitization to psychostimulants and stress after injection of pertussis toxin into the A10 dopamine region J Pharmacol Exp Ther 1991; 259: 916–924

    CAS  PubMed  Google Scholar 

  29. Sorg BA, Steketee JD . Mechanisms of cocaine, induced sensitization Prog Neuropsychopharmacol Biol Psychiatry 1992; 16: 1003–1012

    Article  CAS  PubMed  Google Scholar 

  30. Meiergerd SM, Schenk JO, Sorg BA . Repeated cocaine and stress increase dopamine clearance in the rat medial prefrontal cortex Brain Res 1997; 773: 203–207

    Article  CAS  PubMed  Google Scholar 

  31. Zahrt J, Taylor JR, Mathew RG, Arnsten AF . Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance J Neurosci 1997; 17: 8528–8535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Deutch AY, Clark WA, Roth RH . Prefrontal cortical dopamine depletion enhances the responsiveness of mesolimbic dopamine neurons to stress Brain Res 1990; 521: 311–315

    Article  CAS  PubMed  Google Scholar 

  33. Friedhoff AJ, Carr KD, Uysal S, Schweitzer J . Repeated inescapable stress produces a neuroleptic-like effect on the conditioned avoidance response Neuropsychopharmacology 1995; 13: 129–138

    Article  CAS  PubMed  Google Scholar 

  34. Finlay JM, Zigmond MJ . The effect of stress on central dopaminergic neurons: possible clinical implications Neurochem Res 1997; 22: 1387–1394

    Article  CAS  PubMed  Google Scholar 

  35. MacLean PD . Brain evolution relating to family, play and the separation call Arch Gen Psychiatry 1985; 42: 405–417

    Article  CAS  PubMed  Google Scholar 

  36. Cenci MA, Kalen P, Mandel RJ, Bjorklund A . Regional differences in the regulation of dopamine and noradrenaline release in medial frontal cortex, nucleus accumbens and caudate-putamen: a microdialysis study in the rat Brain Res 1992; 581: 217–228

    Article  CAS  PubMed  Google Scholar 

  37. Cabib S, Puglisi-Allegra S . Stress, depression and the mesolimbic dopamine system Psychopharmacol Berl 1996; 128: 331–342

    Article  CAS  Google Scholar 

  38. Deutch AY, Lee MC, Gillham MH, Cameron DA, Goldstein M, Iadarola MJ . Stress selectively increases fos protein in dopamine neurons innervating the prefrontal cortex Cereb Cortex 1991; 1: 273–292

    Article  CAS  PubMed  Google Scholar 

  39. Keefe KA, Stricker EM, Zigmond MJ, Abercrombie ED . Environmental stress increases extracellular dopamine in striatum of 6-hydroxydopamine-treated rats: in vivo microdialysis studies Brain Res 1990; 527: 350–353

    Article  CAS  PubMed  Google Scholar 

  40. Tidey JW, Miczek KA . Social defeat stress selectively alters mesocorticolimbic dopamine release: an in vivo microdialysis study Brain Res 1996; 721: 140–149

    Article  CAS  PubMed  Google Scholar 

  41. Carlson JN, Fitzgerald LW, Keller RW Jr, Glick SD . Side and region dependent changes in dopamine activation with various durations of restraint stress Brain Res 1991; 550: 313–318

    Article  CAS  PubMed  Google Scholar 

  42. Cabib S, Puglisi-Allegra S . Genotype-dependent effects of chronic stress on apomorphine-induced alterations of striatal and mesolimbic dopamine metabolism Brain Res 1991; 542: 91

    Article  CAS  PubMed  Google Scholar 

  43. Inoue T, Tsuchiya K, Koyama T . Regional changes in dopamine and serotonin activation with various intensity of physical and psychological stress in the rat brain Pharmacol Biochem Behav 1994; 49: 911–920

    Article  CAS  PubMed  Google Scholar 

  44. Deutch AY, Cameron DS . Pharmacological characterization of dopamine systems in the nucleus accumbens core and shell Neuroscience 1992; 46: 49–56

    Article  CAS  PubMed  Google Scholar 

  45. Deutch AY . Prefrontal cortical dopamine systems and the elaboration of functional corticostriatal circuits: implications for schizophrenia and Parkinson's disease J Neural Transm Gen Sect 1993; 91: 197–221

    Article  CAS  PubMed  Google Scholar 

  46. Kalivas PW, Duffy P . Selective activation of dopamine transmission in the shell of the nucleus accumbens by stress Brain Res 1995; 675: 325–328

    Article  CAS  PubMed  Google Scholar 

  47. Jordan S, Kramer GL, Zukas PK, Petty F . Previous stress increases in vivo biogenic amine response to swim stress Neurochem Res 1994; 19: 1521–1525

    Article  CAS  PubMed  Google Scholar 

  48. Gresch PJ, Sved AF, Zigmond MJ, Finlay JM . Stress-induced sensitization of dopamine and norepinephrine efflux in medial prefrontal cortex of the rat J Neurochem 1994; 63: 575–583

    Article  CAS  PubMed  Google Scholar 

  49. Sudha S, Pradhan N . Stress, induced changes in regional monoamine metabolism and behavior in rats Physiol Behav 1995; 57: 1061–1066

    Article  CAS  PubMed  Google Scholar 

  50. Shanks N, Zalcman S, Zacharko RM, Anisman H . Alterations of central norepinephrine, dopamine and serotonin in several strains of mice following acute stressor exposure Pharmacol Biochem Behav 1991; 38: 69–75

    Article  CAS  PubMed  Google Scholar 

  51. Puglisi-Allegra S, Kempf E, Cabib S . Role of genotype in the adaptation of the brain dopamine system to stress Neurosci Biobehav Rev 1990; 14: 523–528

    Article  CAS  PubMed  Google Scholar 

  52. Cabib S, Puglisi-Allegra S . Genotype-dependent effects of chronic stress on apomorphine-induced alterations of striatal and mesolimbic dopamine metabolism Brain Res 1991; 542: 91–96

    Article  CAS  PubMed  Google Scholar 

  53. Puglisi-Allegra S, Kempf E, Schleef C, Cabib S . Repeated stressful experiences differently affect brain dopamine receptor subtypes Life Sci 1991; 48: 1263–1268

    Article  CAS  PubMed  Google Scholar 

  54. Badiani A, Cabib S, Puglisi-Allegra S . Chronic stress induces strain-dependent sensitization to the behavioral effects of amphetamine in the mouse Pharmacol Biochem Behav 1992; 43: 53–60

    Article  CAS  PubMed  Google Scholar 

  55. Kamei H, Kameyama T, Nabeshima T . Activation of both dopamine D1 and D2 receptors necessary for amelioration of conditioned fear stress Eur J Pharmacol 1995; 273: 229–333

    Article  CAS  PubMed  Google Scholar 

  56. Henry C, Guegant G, Cador M, Arnauld E, Arsaut J, Le-Moal M et al. Prenatal stress in rats facilitates amphetamine-induced sensitization and induces long-lasting changes in dopamine receptors in the nucleus accumbens Brain Res 1995; 685: 179–186

    Article  CAS  PubMed  Google Scholar 

  57. Kiyatkin EA, Belyi VP, Rusakov DYU, Maksimov VV, Pankratova NV, Rozhanets VV . Long-term changes of striatal D-2 receptors in rats chronically exposed to morphine under aversive life conditions Int J Neurosci 1991; 58: 55–61

    Article  CAS  PubMed  Google Scholar 

  58. Tomic M, Joksimovic J . Glucocorticoid status affects the response of rat striatal dopamine D2 receptors to hyperthermia and turpentine treatment Endocr Regul 1991; 25: 225–230

    CAS  PubMed  Google Scholar 

  59. Papp M, Klimek V, Willner P . Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress, induced anhedonia and its reversal by imipramine Psychopharmacol Berl 1994; 115: 441–446

    Article  CAS  Google Scholar 

  60. Steketee JD, Kalivas PW . Sensitization to psychostimulants and stress after injection of pertussis toxin into the A10 dopamine region J Pharmacol Exp Ther 1991; 259: 916–924

    CAS  PubMed  Google Scholar 

  61. Fontenot MB, Kaplan JR, Manuck SB, Arango V, Mann JJ . Long-term effects of chronic social stress on serotonergic indices in the prefrontal cortex of adult male cynomolgus macaques Brain Res 1995; 705: 105–108

    Article  CAS  PubMed  Google Scholar 

  62. Kelland MD, Chiodo LA . Serotonergic modulation of midbrain dopamine systems. In: Ashby CA Jr (ed) The Modulation of Dopaminergic Neurotransmission by Other Neurotransmitters CRC Press: Boca Raton 1996; pp87–122

    Google Scholar 

  63. Shively CA, Grant KA, Ehrenkaufer RL, Mach RH, Nader MA . Social stress, depression, and brain dopamine in female cynomolgus monkeys Ann NY Acad Sci 1997; 15: 574–577

    Article  Google Scholar 

  64. Feenstra MG, Kalsbeek A, Van-Galen H . Neonatal lesions of the ventral tegmental area affect monoaminergic responses to stress in the medial prefrontal cortex and other dopamine projection areas in adulthood Brain Res 1992; 596: 169–182

    Article  CAS  PubMed  Google Scholar 

  65. Cabib S, Puglisi-Allegra S, D'Amato FR . Effects of postnatal stress on dopamine mesolimbic system responses to aversive experiences in adult life Brain Res 1993; 604: 232–239

    Article  CAS  PubMed  Google Scholar 

  66. Lipska BK, Chrapusta SJ, Egan MF, Weinberger DR . Neonatal excitotoxic ventral hippocampal damage alters dopamine response to mild repeated stress and to chronic haloperidol Synapse 1995; 20: 125–130

    Article  CAS  PubMed  Google Scholar 

  67. Inglefield JR, Kellogg CK . Hypothalamic GABAA receptor blockade modulates cerebral cortical systems sensitive to acute stressors Psychopharmacol Berl 1994; 116: 339–345

    Article  CAS  Google Scholar 

  68. Biggio G, Concas A, Corda MG, Giorgi O, Sanna E, Serra M . GABAergic and dopaminergic transmission in the rat cerebral cortex: effect of stress, anxiolytic and anxiogenic drugs Pharmacol Ther 1990; 48: 121–142

    Article  CAS  PubMed  Google Scholar 

  69. Boireau A, Dubedat P, Laduron PM, Doble A, Blanchard JC . Preferential decrease in dopamine utilization in prefrontal cortex by zopiclone, diazepam and zolpidem in unstressed rats J Pharm Pharmacol 1990; 42: 562–565

    Article  CAS  PubMed  Google Scholar 

  70. Kaneyuki H, Yokoo H, Tsuda A, Yoshida M, Mizuki Y, Yamada M et al. Psychological stress increases dopamine turnover selectively in mesoprefrontal dopamine neurons of rats: reversal by diazepam Brain Res 1991; 557: 154–161

    Article  CAS  PubMed  Google Scholar 

  71. Grobin AC, Roth RH, Deutch AY . Regulation of the prefrontal cortical dopamine system by the neuroactive steroid 3a,21-dihydroxy-5a-pregnane-20-one Brain Res 1992; 578: 351–356

    Article  CAS  PubMed  Google Scholar 

  72. Hegarty AA, Vogel WH . Modulation of the stress response by ethanol in the rat frontal cortex Pharmacol Biochem Behav 1993; 45: 327–334

    Article  CAS  PubMed  Google Scholar 

  73. Dazzi L, Motzo C, Imperato A, Serra M, Gessa GL, Biggio G . 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 J Pharmacol Exp Ther 1995; 273: 241–247

    CAS  PubMed  Google Scholar 

  74. Wedzony K, Mackowiak M, Fijal K, Golembiowska K . Evidence that conditioned stress enhances outflow of dopamine in rat prefrontal cortex: a search for the influence of diazepam and 5-HT1A agonists Synapse 1996; 24: 240–247

    Article  CAS  PubMed  Google Scholar 

  75. Finlay JM, Zigmond MJ . The effect of stress on central dopaminergic neurons: possible clinical implications Neurochem Res 1997; 22: 1387–1394

    Article  CAS  PubMed  Google Scholar 

  76. Morrow BA, Clark WA, Roth RH . Stress activation of mesocorticolimbic dopamine neurons: effects of a glycine/NMDA receptor antagonist Eur J Pharmacol 1993; 238: 255–262

    Article  CAS  PubMed  Google Scholar 

  77. Goldstein LE, Rasmusson AM, Bunney BS, Roth RH . The NMDA glycine site antagonist (+)-HA-966 selectively regulates conditioned stress-induced metabolic activation of the mesoprefrontal cortical dopamine but not serotonin systems: a behavioral, neuroendocrine, and neurochemical study in the rat J Neurosci 1994; 14: 4937–4950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Keefe KA, Sved AF, Zigmond MJ, Abercrombie ED . Stress-induced dopamine release in the neostriatum: evaluation of the role of action potentials in nigrostriatal dopamine neurons or local initiation by endogenous excitatory amino acids J Neurochem 1993; 61: 1943–1952

    Article  CAS  PubMed  Google Scholar 

  79. Jedema HP, Moghaddam B . Glutamatergic control of dopamine release during stress in the rat prefrontal cortex J Neurochem 1994; 63: 785–788

    Article  CAS  PubMed  Google Scholar 

  80. Doherty MD, Gratton A . NMDA receptors in nucleus accumbens modulate stress-induced dopamine release in nucleus accumbens and ventral tegmental area Synapse 1997; 26: 225–234

    Article  CAS  PubMed  Google Scholar 

  81. Jaskiw GE, Karoum FK, Weinberger DR . Persistent elevations in dopamine and its metabolites in the nucleus accumbens after mild subchronic stress in rats with ibotenic acid lesions of the medial prefrontal cortex Brain Res 1990; 534: 321–323

    Article  CAS  PubMed  Google Scholar 

  82. Hutson PH, Barton CL . L-701,324, a glycine/NMDA receptor antagonist, blocks the increase of cortical dopamine metabolism by stress and DMCM Eur J Pharmacol 1997; 326: 127–132

    Article  CAS  PubMed  Google Scholar 

  83. Piazza PV, Le Moal MI . The role of stress in drug self-administration TIPS 1998; 19: 67–74

    CAS  PubMed  Google Scholar 

  84. De-Kloet ER, Rots NY, Cools AR . Brain-corticosteroid hormone dialogue: slow and persistent Cell Mol Neurobiol 1996; 16: 345–356

    Article  CAS  PubMed  Google Scholar 

  85. Henry C, Guegant G, Cador M, Arnauld E, Arsaut J, Le Moal M et al. Prenatal stress in rats facilitates amphetamine-induced sensitization and induces long-lasting changes in dopamine receptors in the nucleus accumbens Brain Res 1995; 685: 179–186

    Article  CAS  PubMed  Google Scholar 

  86. Alonso SJ, Navarro E, Rodriguez M . Permanent dopaminergic alterations in the n. accumbens after prenatal stress Pharmacol Biochem Behav 1994; 49: 353–358

    Article  CAS  PubMed  Google Scholar 

  87. Piazza PV, Le Moal ML . Pathophysiological basis of vulnerability to drug abuse: role of an interaction between stress, glucocorticoids, and dopaminergic neurons Annu Rev Pharmacol Toxicol 1996; 36: 359–378

    Article  CAS  PubMed  Google Scholar 

  88. Steketee JD, Kalivas PW . Sensitization to psychostimulants and stress after injection of pertussis toxin into the A10 dopamine region J Pharmacol Exp Ther 1991; 259: 916–924

    CAS  PubMed  Google Scholar 

  89. Rouge Pont F, Marinelli M, Le Moal M, Simon H, Piazza PV . Stress, induced sensitization and glucocorticoids. II. Sensitization of the increase in extracellular dopamine induced by cocaine depends on stress, induced corticosterone secretion J Neurosci 1995; 15: 7189–7995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Prasad BM, Sorg BA, Ulibarri C, Kalivas PW . Sensitization to stress and psychostimulants. Involvement of dopamine transmission versus the HPA axis Ann NY Acad Sci 1995; 771: 617–625

    Article  CAS  PubMed  Google Scholar 

  91. Deroche V, Marinelli M, Maccari S, Le Moal M, Simon H, Piazza PV . Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion J Neurosci 1995; 15: 7181–7188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Sorg BA, Kalivas PW . Effects of cocaine and footshock stress on extracellular dopamine levels in the ventral striatum Brain Res 1991; 559: 29–36

    Article  CAS  PubMed  Google Scholar 

  93. Sorg BA, Kalivas PW . Effects of cocaine and footshock stress on extracellular dopamine levels in the medial prefrontal cortex Neuroscience 1993; 53: 695–703

    Article  CAS  PubMed  Google Scholar 

  94. Hamamura T, Fibiger HC . Enhanced stress-induced dopamine release in the prefrontal cortex of amphetamine-sensitized rats Eur J Pharmacol 1993; 237: 65–71

    Article  CAS  PubMed  Google Scholar 

  95. Diaz Otanez CS, Capriles NR, Cancela LM . D1 and D2 dopamine and opiate receptors are involved in the restraint stress-induced sensitization to the psychostimulant effects of amphetamine Pharmacol Biochem Behav 1997; 58: 9–14

    Article  CAS  PubMed  Google Scholar 

  96. Hegarty AA, Vogel WH . Modulation of the stress response by ethanol in the rat frontal cortex Pharmacol Biochem Behav 1993; 45: 327–334

    Article  CAS  PubMed  Google Scholar 

  97. Matsuguchi N, Ida Y, Shirao I, Tsujimaru S . Blocking effects of ethanol on stress, induced activation of rat mesoprefrontal dopamine neurons Pharmacol Biochem Behav 1994; 48: 297–299

    Article  CAS  PubMed  Google Scholar 

  98. Koechling UM, Amit Z . Effects of CA antagonists on ethanol-induced excitation in habituated and nonhabituated mice: interaction with stress factors? Pharmacol Biochem Behav 1993; 44: 791–796

    Article  CAS  PubMed  Google Scholar 

  99. Berman SM, Noble EP . The D2 dopamine receptor (DRD2) gene and family stress; interactive effects on cognitive functions in children Behav Genet 1997; 27: 33–43

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L Pani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pani, L., Porcella, A. & Gessa, G. The role of stress in the pathophysiology of the dopaminergic system. Mol Psychiatry 5, 14–21 (2000). https://doi.org/10.1038/sj.mp.4000589

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4000589

Keywords

This article is cited by

Search

Quick links