The regulation of subcortical dopamine systems by the prefrontal cortex: interactions of central dopamine systems and the pathogenesis of schizophrenia

  • A. Y. Deutch
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 36)


A recent hypothesis of the pathogenesis of schizophrenia posits a developmentally-specific dysfunction of the dopaminergic innervation of the prefrontal cortex (PFC; Weinberger, 1987; Berman and Weinberger, 1990). It has been difficult to reconcile this hypothesis with the observation that all clinically effective antipsychotic drugs used for the treatment of schizophrenia block dopamine D2 receptors (see Deutch et al., 1991a). A resolution between the suggestion of functional dopamine (DA) “depletion” in the PFC and enhanced subcortical DA function was offered by studies of Carter, Pycock, and associates (Carter and Pycock, 1980; Pycock et al., 1980a,b). These investigators reported that depletion of DA in the rat PFC enhanced DA utilization in subcortical sites such as the nucleus accumbens septi (NAS) and striatum. Thus, a functional deficit in DA neurotransmission in the PFC would increase subcortical DA turnover, and the D2 receptor blockade induced by antipsychotic drugs would counteract the increase in dopaminergic tone in subcortical sites. This hypothesis has been particularly influential because it incorporates both an explanation for negative symptoms, which are thought to reflect cortical dysfunction (a derangement in DA transmission in the PFC), and the efficacy of anti-psychotic drugs in the treatment of positive symptoms (arising from increases in subcortical DA tone).

As attractive as this hypothesis has been, the physiological underpinnings that subserve such system interactions have remained elusive. Pycock, Carter, and colleagues (Carter and Pycock, 1980; Pycock et al., 1980a,b) reported that 6-hydroxydopamine (6-OHDA) lesions of the PFC increase DA levels and DA turnover in the striatum; certain aspects of their findings have been confirmed (Martin-Iversen et al., 1986; Leccese and Lyness, 1987; Haroutounian et al., 1988). However, other groups have been unable to confirm either the biochemical or behavioral findings of Pycock and associates (Joyce et al., 1983; Oades et al., 1986; Deutch et al., 1990). Moreover, Pycock and colleagues did not observe consistent effects of PFC DA deafferentation on various indices of subcortical DA function (Carter and Pycock, 1980; Pycock et al., 1980a,b). In light of the importance that such DA system interactions may have in the pathogenesis of schizophrenia, we have reinvestigated the effects of cortical DA lesions on subcortical DA function.


Ventral Tegmental Area Dorsal Striatum Excitatory Amino Acid Receptor Dopaminergic Innervation Infralimbic Cortex 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agnati LF, Andersson K, Wiesel F, Fuxe K (1979) A method to determine dopamine levels and turnover rate in discrete nerve terminal systems by quantitative use of dopamine histofluorescence obtained by the Falck-Hillarp methodology. J Neurosci Methods 1: 365–373PubMedCrossRefGoogle Scholar
  2. Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. TINS 13: 266–271PubMedGoogle Scholar
  3. Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 9: 357–381PubMedCrossRefGoogle Scholar
  4. Andreason NC, Flaum M, Swayze VW, Tyrell G, Arndt S (1990) Positive and negative symptoms in schizophrenia: a critical reappraisal. Arch Gen Psychiatry 47: 615–621CrossRefGoogle Scholar
  5. Barbieto L, Cheramy A, Godeheu G, Desce JM, Glowinski J (1990) Glutamate receptors of a quisqualate-kainate subtype are involved in the presynaptic regulation of dopamine release in the cat caudate nucleus in vivo. Eur J Neurosci 2: 304–311CrossRefGoogle Scholar
  6. Bartholini G (1976a) Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. J Pharm Pharmacol 28: 429–433PubMedCrossRefGoogle Scholar
  7. Bartholini G (1976b) Preferential effect of noncataleptogenic neuroleptics on mesocortical dopaminergic function. Adv Biochem Psychopharmacol 16: 607–611Google Scholar
  8. Beaudet, Wolfe (1992) Morphological substrate for neurotensin-dopamine interactions in the rat midbrain tegmentum. Ann NY Acad Sci (in press)Google Scholar
  9. Beckstead RM (1979) An autoradiographic examination of corticocortical and sub-cortical projections of the mediodorsal-projection (prefrontal) cortex in the rat. J Comp Neurol 184: 43–62PubMedCrossRefGoogle Scholar
  10. Benes FM, McSparren J, Bird ED, SanGiovanni JP, Vincent SL (1991) Deficits in small interneurons in prefrontal and cingulate cortex of schizophrenic and schizo-affective patients. Arch Gen Psychiatry 48: 996–1001PubMedCrossRefGoogle Scholar
  11. Benes FM, Vincent SL, Alsterberg G, Bird ED, SanGiovanni JP (1992) Increased GABA-A receptor binding in superficial layers of schizophrenic cingulate cortex. J Neurosci 12: 924–929PubMedGoogle Scholar
  12. Bennett JP, Leslie CA (1990) NMDA receptors modulate striatal dopamine release and metabolism in vivo: a microdialysis study. Soc Neurosci Abstr 16: 679Google Scholar
  13. Berger B, Verney C (1984) Development of the catecholamine innervation in rat neocortex: morphological features. In: Descarries L, Reader TR, Jasper HH (eds) Monoamine innervation of the cerebral cortex. Alan R Liss, New York, pp 95–121Google Scholar
  14. Berger B, Gaspar P, Verney C (1991) Dopaminergic innervation of the cerebral cortex: unexpected differences between rodents and primates. Trends Neurosci 14: 21–27PubMedCrossRefGoogle Scholar
  15. Berman KF, Weinberger D (1990) Thre prefrontal cortex in schizophrenia and other neuropsychiatric disease: in vivo physiological correlates of cognitive deficits. In: Uylings HBM, Van Eden CG, De Bruin JPC, Corner MA, Feenstra MPG (eds) The prefrontal cortex: its structure, function, and pathology. Elsevier Science Publishers, Amsterdam, pp 521–538 (Prog Brain Res 85 )Google Scholar
  16. Bertolucci-D’Angio M, Serrano A, Driscoll P, Scatton B (1990) Involvement of mesocorticolimbic dopaminergic systems in emotional states. In: Uylings HBM, Van Eden CG, De Bruin JPC, Corner MA, Feenstra MPG (eds) The prefrontal cortex: its structure, function, and pathology. Elsevier Science Publishers, Amsterdam, pp 405–418 (Prog Brain Res 85 )Google Scholar
  17. Black IB, Green SC (1975) Postmortem changes in brain catecholamine enzymes. Arch Neurol 32: 47–49PubMedCrossRefGoogle Scholar
  18. Bleuler E (1950) Dementia praecox or the group of schizophrenias (Zinkin J, trans). International Universities Press, New YorkGoogle Scholar
  19. Bolam JP (1984) Synapses of identified neurons in the neostriatum. In: Evered D, O’Connor M (eds) Functions of the basal ganglia. Pittman Press, London, pp 42–57 (Ciba Foundation Symposium 107 )Google Scholar
  20. Bouyer JJ, Park DH, Joh TH, Pickel VM (1984) Chemical and structural analysis of the relation between cortical inputs and tyrosine hydroxylase-containing terminals in rat neostriatum. Brain Res 302: 267–275PubMedCrossRefGoogle Scholar
  21. Braszko JJ, Bannon MJ, Bunney BS, Roth RH (1981) Intra-striatal kainic acid: acute effects on electrophysiological and biochemical measures of nigrostriatal dopaminergic activity. J Pharmacol Exp Ther 216: 289–293PubMedGoogle Scholar
  22. Brog JM, Deutch AY, Zahm DS (1991) Afferent projections to the nucleus accumbens core and shell in the rat. Soc Neurosci Abstr 17: 454Google Scholar
  23. Brown GW, Birley JLP, Wing JK (1972) Influence of family life on the course of schizophrenic illness: a replication. Br J Psychiatry 14: 241–252CrossRefGoogle Scholar
  24. Bunney BS, Aghajanian GK (1976) Dopamine and norepinephrine innervated cells in the rat prefrontal cortex: pharmacological differentiation using micro-iontophoretic techniques. Life Sci 19: 1783–1792PubMedCrossRefGoogle Scholar
  25. Bunney BS, Chiodo LA (1984) Mesocortical dopamine systems: further electrophysiological and pharmacological characterization. In: Descarries L, Reader TR, Jasper HH (eds) Monoamine innervation of the cerebral cortex. Alan R Liss, New York, pp 263–278Google Scholar
  26. Carpenter WT Jr (1991) Psychopathology and common sense: where we went wrong with negative symptoms. Biol Psychiatry 29: 735–737PubMedCrossRefGoogle Scholar
  27. Carter CJ (1982) Topographical distribution of possible glutamatergic pathways from the frontal cortex to the striatum and substantia nigra in rats. Neuropharmacology 21: 383–393CrossRefGoogle Scholar
  28. Carter CJ, Pycock CJ (1980) Behavioral and biochemical effects of dopamine and noradrenaline depletion within the medial prefrontal cortex of the rat. Brain Res 192: 163–176PubMedCrossRefGoogle Scholar
  29. Cheramy A, Romo R, Glowinski J (1984) Role of corticostriatal glutamatergic neurons in the presynaptic control of dopamine release. In: Sandler M, Feuerstein C, Scatton B (eds) Neurotransmitter interactions in the basal ganglia. Raven Press, New York, pp 133–141Google Scholar
  30. Cheramy A, Romo R, Godehu G, Baruch P, Glowinski J (1986) In vivo presynaptic control of dopamine release in the cat caudate nucleus. II. Facilitatory or inhibitory influence of L-glutamate. Neuroscience 19: 1081–1090PubMedCrossRefGoogle Scholar
  31. Chesselet M-F (1984) Presynaptic regulation of neurotransmitter release in the brain: facts and hypotheses. Neuroscience 12: 347–375PubMedCrossRefGoogle Scholar
  32. Christie NJ, Bridge S, James LB, Beart PM (1985) Excitotoxic lesions suggest an aspartatergic projection from rat medial prefrontal cortex to ventral tegmental area. Brain Res 333: 169–172PubMedCrossRefGoogle Scholar
  33. Clow DW, Jhamandas K (1989) Characterization of L-glutamate action on the release of endogenous dopamine from the rat caudate-putamen. J Pharmacol Exp Ther 284: 722–728Google Scholar
  34. Consolo S, Landinski H, Bianchi S, Ghezzi D (1977) Apparent lack of a dopaminergiccholinergic link in the rat nucleus accumbens septi-tuberculum olfactorium. Brain Res 135: 255PubMedCrossRefGoogle Scholar
  35. Cox DWG, Headley MH, Watkins JC (1977) Actions of L- and D-homocysteate in rat CNS: a correlation between low-affinity uptake and the time courses of exciation by microiontophoretically applied L-glutamate analogues. J Neurochem 29: 579–588PubMedCrossRefGoogle Scholar
  36. Czernansky JG, Murphy GM, Faustman WO (1991) Limbic/mesolimbic connections and the pathogenesis of schizophrenia. Biol Psychiatry 30: 383–400CrossRefGoogle Scholar
  37. Deutch AY (1991) Heterogeneity of the prefrontal cortical dopamine system in responsiveness to stress. Soc Neurosci Abstr 17: 529Google Scholar
  38. Deutch AY, Roth RH (1990) The determinants of stress-induced activation of the prefrontal cortical dopamine system. In: Uylings HBM, Van Eden CG, De Bruin JPC, Corner MA, Feenstra MPG (eds) The prefrontal cortex: its structure, function, and pathology. Elsevier Science Publishers, Amsterdam, pp 367–393 (Prog Brain Res 85 )Google Scholar
  39. Deutch AY, Cameron DS (1992) Pharmacological characterization of dopamine systems in the nucleus accumbens core and shell. Neuroscience 46: 49–56PubMedCrossRefGoogle Scholar
  40. Deutch AY, Zahm DS (1992) The current status of neurotensin-dopamine interactions: issues and speculations. Ann NY Acad Sci (in press)Google Scholar
  41. Deutch AY, Tam S-Y, Roth RH (1985) Footshock and conditioned stress increase 3,4dihydroxyphenylacetic acid ( DOPAC) in the ventral tegmental area but not sub-stantia nigra. Brain Res 333: 143–146PubMedCrossRefGoogle Scholar
  42. Deutch AY, Goldstein M, Baldino F Jr, Roth RH (1988) The telencephalic projections of the A8 dopamine cell group. Ann NY Acad Sci 537: 27–50PubMedCrossRefGoogle Scholar
  43. Deutch AY, Clark WA, Roth RH (1990) Prefrontal cortical dopamine depletion enhances the responsiveness of mesolimbic dopamine neurons to stress. Brain Res 521: 311–315PubMedCrossRefGoogle Scholar
  44. Deutch AY, Moghaddam B, Innis R, Krystal JH, Aghajanian GK, Bunney BS, Charney DS (1991a) Mechanisms of action of atypical antipsychotic drugs: implications for novel therapeutic strategies for schizophrenia. Schizophr Res 4: 121–156PubMedCrossRefGoogle Scholar
  45. Deutch AY, Lee MC, Gillham MH, Cameron D, Goldstein M, Iadorola MJ (1991b) Stress selectively increases Fos protein in dopamine neurons innervating the prefrontal cortex. Cerebral Cortex 1: 273–292PubMedCrossRefGoogle Scholar
  46. Do KQ, Herrling PL, Streit P, Turski WA, Cuenod M (1986) In vitro release and electrophysiological effects in situ of homocysteic acid, an endogenous N-methyl(D)-aspartic agonist in the mammalian striatum. J Neurosci 6: 2226–22341PubMedGoogle Scholar
  47. Donoghue JP, Herkenham M (1986) Neostriatal projections from individual cortical fields conform to histochemically distinct striatal compartments in the rat. Brain Res 365: 397–403PubMedCrossRefGoogle Scholar
  48. Elsworth JD, Deutch AY, Redmond DE Jr, Sladek JR Jr, Roth RH (1990) MPTP reduces dopamine and norepinephrine concentrations in the supplementary motor area and cingulate cortex of the primate. Neurosci Lett 114: 316–312PubMedCrossRefGoogle Scholar
  49. Errami M, Nieoullon A (1986) Development of a micromethod to study the Nat-independent L-[3H]glutamic acid binding to rat striatal membranes. I. Biochemical and pharmacological characterization. Brain Res 366: 169–177PubMedCrossRefGoogle Scholar
  50. Friedemann MN, Gerhardt GA (1990) The effects of excitatory amino acids on dopamine nerve terminals in the neostriatum of the anesthetized rat: an in vivo electrochemical study. Soc Neurosci Abstr 16: 584Google Scholar
  51. Fuxe K, Fredholm BB, Agnati LF, Corrodi H (1978) Dopamine receptors and ergot drugs. Evidence that an ergolene derivative is a differential agonist at subcortical limbic dopamine receptors. Brain Res 146: 295–311PubMedCrossRefGoogle Scholar
  52. Gariano RF, Groves PM (1988) Burst firing induced in midbrain dopamine neurons by stimulation of the medial prefrontal and anterior cingulate cortices. Brain Res 462: 194–198PubMedCrossRefGoogle Scholar
  53. Gerfen CR (1989) The neostriatal mosaic: striatal patch-matrix organization is related to cortical lamination. Science 246: 385–388PubMedCrossRefGoogle Scholar
  54. Gerfen CR, Herkenham M, Thibault J (1987) The neostriatal mosaic. II. Patch-and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems. J Neurosci 7: 3915–3934PubMedGoogle Scholar
  55. Giorguieff MF, Kernel ML, Glowinski J (1977) Presynaptic effect of L-glutamatic acid on the release of dopamine in rat striatal slices. Neurosci Lett 6: 73–77PubMedCrossRefGoogle Scholar
  56. Girault JA, Spampinato U, Glowinski J, Besson MJ (1986) In vivo release of [3H]yaminobutyric acid in the rat neostriatum. II. Opposing effects of Dl and D2 dopamine receptor stimulation in the dorsal caudate putamen. Neuroscience 19: 1109–1117PubMedCrossRefGoogle Scholar
  57. Girault JA, Spampinato U, Savaki HE, vlowinski J, Besson MJ (1986) In vivo release of [3H]y-aminobutyric acid in the rat neostriatum. I. Characterization and topographical heterogeneity of the effects of dopaminergic and cholinergic agents. Neuroscience 19: 1100–1108Google Scholar
  58. Goldstein M, Deutch AY (1992) Dopaminergic mechanisms in the pathogenesis of schizophrenia. FASEB J 6: 2413–2421PubMedGoogle Scholar
  59. Goldstein M, Lieberman AN, Helmer E, Koslow M, Ransohoff J, Elsworth JD, Roth RH, Deutch AY (1988) Biochemical analysis of caudate nucleus biopsy samples from parkinsonian patients. Ann Neurol 24: 685–688PubMedCrossRefGoogle Scholar
  60. Goldman-Rakic PS, Leranth C, Williams SM, Mons N, Geffard M (1989) Dopamine synaptic complex with pyramidal neurons in primate cerebral cortex. Proc Natl Acad Sci USA 86: 9015–9019PubMedCrossRefGoogle Scholar
  61. Grace AA (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41: 1–24PubMedCrossRefGoogle Scholar
  62. Graybiel AM (1984) Correspondence between the dopamine islands and striosomes of the mammalian striatum. Neuroscience 13: 1157–1187PubMedCrossRefGoogle Scholar
  63. Gutman CR, Booze RM, Davis JN (1987) Benefits of rapid vs. delayed autopsy in human brain catecholamine axonal morphology. Soc Neurosci Abstr 13: 437Google Scholar
  64. Haroutunian V, Knott P, Davis KL (1988) Effects of mesocortical dopaminergic lesions upon subcortical dopaminergic function. Psychopharmacol Bull 24: 341–344PubMedGoogle Scholar
  65. Hefti F, Melamed E, Wurtman RJ (1980) Partial lesions of the nigrostriatal system in rat brain: biochemical characterization. Brain Res 195: 123–137PubMedCrossRefGoogle Scholar
  66. Heimer L, Zahm DS, Churchill L, Kalivas PW, Wohltmann C (1991) Specificity in the projection patterns of the accumbal core and shell. Neuroscience 41: 89–126PubMedCrossRefGoogle Scholar
  67. Herkenham M (1991) Mismatches between neurotransmitter and receptor localizations: implications for endocrine functions in brain. In: Fuxe K, Agnati LF (eds) Volume transmission in the brain: novel mechanisms for neural transmission. Raven Press, New York, pp 63–87Google Scholar
  68. Imperato A, Honore T, Jensen LH (1990) Dopamine release in the nucleus caudatus and in nucleus accumbens in under glutamatergic control through non-NMDA receptors: a study in freely moving rats. Brain Res 530: 223–228PubMedCrossRefGoogle Scholar
  69. Jaskiw GE, Weinberger DR, Crawley JN (1991) Microinjection of apomorphine into the prefrontal cortex of the rat reduces dopamine metabolite concentrations in microdialysate from the caudate nucleus. Biol Psychiatry 29: 703–706PubMedCrossRefGoogle Scholar
  70. Jhamandas K, Marien M (1987) Glutamate-evoked release of endogenous brain dopamine: inhibition by an excitatory amino acid antagonist and an enkephalin analogue. Br J Pharmacol 90: 641–650PubMedGoogle Scholar
  71. Joyce EM, Stinus L, Iversen SD (1983) Effect of injections of 6-hydroxydopamine into either nucleus accumbens septi or frontal cortex on spontaneous and drug-induced activity. Neuropharmacology 9: 1141–1145CrossRefGoogle Scholar
  72. Julou L, Scatton B, Glowinski J (1976) Acute and chronic treatments with neuroleptics: similarities and differences in their action on nigrostriatal, mesolimbic, and mesocortical dopaminergic neurons. Adv Biochem Psychopharmacol 16: 617–624Google Scholar
  73. Kalivas PW, Duffle P (1990) Effect of acute and daily neurotensin and enkephalin treatment on extracellular dopamine in the nucleus accumbens. J Neurosci 10: 2940–2949PubMedGoogle Scholar
  74. Keefe KA, Zigmond MJ, Abercrombie ED (1990) In vivo evidence that basal dopamine efflux in striatum is not regulated by endogenous excitatory amino acids. Soc Neurosci Abstr 16: 522Google Scholar
  75. Kilpatrick IC, Mozely LS (1986) An intial analysis of the regional distribution of excit- atory sulphur-containing amino acids in the rat brain. Neurosci Lett 72: 189–193PubMedCrossRefGoogle Scholar
  76. Kim JM, Hassler R, Haus P, Paik KS (1977) Effect of frontal cortical ablation on striatal glutamic acid level in the rat. Brain Res 132: 370–374PubMedCrossRefGoogle Scholar
  77. Knopfel T, Zeise ML, Cuenod M, Ziegelgansberger W (1987) L-Homocysteic acid but not L-glutamate is an endogenous N-methyl-D-aspartic acid receptor preferring agonist in rat neocortical neurons in vitro. Neurosci Lett 81: 188–192PubMedCrossRefGoogle Scholar
  78. Knorr AM, Deutch AY, Roth RH (1989) The anxiogenic ß-carboline FG 7142 increases in vivo and in vitro tyrosine hydroxylation in the prefrontal cortex. Brain Res 495: 355–361PubMedCrossRefGoogle Scholar
  79. Krebs MO, Desce JM, Kernel ML, Gauchy C, Godeheu G, Cheramy A, Glowinski J (1991) Glutamatergic control of dopamine release in the rat striatum: evidence for presynaptic N-methyl-D-aspartate receptors on dopaminergic nerve terminals. J Neurochem 56: 81–85PubMedCrossRefGoogle Scholar
  80. Leccese AP, Lyness WH (1987) Lesions of dopamine neurons in the medial prefrontal cortex: effects on self-administration of amphetamine and dopamine synthesis in the brain of the rat. Neuropharmacology 26: 1303–1308PubMedCrossRefGoogle Scholar
  81. Lehmann J, Tsai C, Wood PL (1988) Homocysteic acid as a putative excitatory amino acid neurotransmitter. I. Postsynaptic characteristics at N-methyl-D-aspartate-type receptors on striatal cholinergic interneurons. J Neurochem 51: 1765–1770PubMedCrossRefGoogle Scholar
  82. Lonart G, Zigmond MJ (1991) High glutamate concentrations evoke Caindependent dopamine release from striatal slices: a possible role of reverse dopamine transport. J Pharmacol Exp Ther 256: 1132–1138PubMedGoogle Scholar
  83. Louilot A, Taghzouti K, Demineire JM, Simon H, Le Moal M (1987) Dopamine and behavior: functional and theoretical considerations. In: Sandler M, Feuerstein C, Scatton B (eds) Neurotransmitter interactions in the basal ganglia. Raven Press, New YorkGoogle Scholar
  84. Louilot A, Le Moal M, Simon H (1989) Opposite influences of dopaminergic pathways to the prefrontal cortex or the septum on dopaminergic transmission in the nucleus accumbens. An in vivo voltammetric study. Neuroscience 29: 45–56PubMedCrossRefGoogle Scholar
  85. Mantz J, Thierry AM, Glowinski J (1989) Effect of noxious tail pinch on the discharge rate of mesocortical and mesolimbic dopamine neurons: selective activation of the mesocortical system. Brain Res 476: 377–381PubMedCrossRefGoogle Scholar
  86. Marien M, Brien J, Jhamandas K (1983) Regional release of [3H]dopamine from rat brain in vitro: effects of opiates on release induced by potassium, nicotine, and L-glutamic acid. Can J Physiol Pharmacol 61: 43–60PubMedCrossRefGoogle Scholar
  87. Martin-Iversen MT, Szostak C, Fibiger HC (1986) 6-Hydroxydopamine lesions of the medial prefrontal cortex fail to influence intravenous self-administration of cocaine. Psychopharmacology 88: 310–314Google Scholar
  88. Mayer ML, Viklicky L (1989) Concanavalin A selectively reduces desensitization of mammalian neuronal quisqualate receptors. Proc Natl Acad Sci USA 86: 1411–1415PubMedCrossRefGoogle Scholar
  89. McGeer PL, McGeer EG, Scherrer U, Singh K (1977) A glutamatergic cortico-striatal path? Brain Res 128: 369–373PubMedCrossRefGoogle Scholar
  90. McGeorge AJ, Faull RLM (1989) The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience 29: 503–537PubMedCrossRefGoogle Scholar
  91. Moghaddam B, Bunney BS (1990a) Acute effect of typical and atypical antipsychotic drugs on the release of dopamine from the prefrontal cortex, nucleus accumbens, and striatum of the rat: an in vivo microdialysis study. J Neurochem 54: 1755–1760 Moghaddam B, Gruen RJ (1991) Do endogenous excitatory amino acids influence striatal dopamine release? Brain Res 544: 329–330Google Scholar
  92. Moghaddam B, Gruen RJ, Roth RH, Bunney BS, Adams RN (1990b) Effect of L-glutamate on the release of striatal dopamine: in vivo dialysis and electrochemical studies. Brain Res 518: 55–60PubMedCrossRefGoogle Scholar
  93. Morgan JI, Curran T (1986) The role of ion flux in the control of c-fos. Nature 322: 552–555PubMedCrossRefGoogle Scholar
  94. Nicholson IR, Neufeld RWJ (1989) Forms and mechanisms of susceptibility to stress in schizophrenia. In: Neufeld RWJ (ed) Advances in the investigation of psychological/stress. Wiley, New York, pp 392–420Google Scholar
  95. Oades RD, Tagzhouti K, Rivet J-M, Simon H, Le Moal M (1986) Locomotor activity in relation to dopamine and noradrenaline in the nucleus accumbens, septal, and frontal areas: a 6-hydroxydopamine study. Neuropsychobiology 16: 37–42PubMedCrossRefGoogle Scholar
  96. Olson L, Seiger A, Fuxe F (1972) Heterogeneity of striatal and limbic dopamine innervation: highly fluorescent islands in developing and adult rats. Brain Res 44: 283–288PubMedCrossRefGoogle Scholar
  97. Palmer AM, Hutson PH, Lowe SL, Bowen DM (1989) Extracellular concentration of aspartate and glutamate in rat neostriatum following chemical stimulation of frontal cortex. Exp Brain Res 75: 659–663PubMedCrossRefGoogle Scholar
  98. Passingham RE, Myers C, Rawlins N, Lightfoot V, Fearn S (1988) Premotor cortex in the rat. Behav Neurosci 102: 101–109PubMedCrossRefGoogle Scholar
  99. Payson MM, Donzanti BA (1990) Effects of excitatory amino acids on in vivo dopamine release and metabolism in the nucleus accumbens. Soc Neurosci Abstr 16: 584Google Scholar
  100. Penit-Soria J, Audinat E, Crepel F (1987) Excitation of rat prefrontal cortical neurons by dopamine: an in vitro eletrophysiological study. Brain Res 425: 363–374CrossRefGoogle Scholar
  101. Peterson OT, St Mary JS, Harding NR (1987) Cis-flupenthixol antagonism of the rat prefrontal cortex neuronal response to apomorphine and ventral tegmental area input. Brain Res Bull 18: 723–729PubMedCrossRefGoogle Scholar
  102. Pycock CJ, Carter CJ, Kerwin RW (1980a) Effect of 6-hydroxydopamine lesions of the medial prefrontal cortex on neurotransmitter systems in subcortical sites in the rat. J Neurochem 34: 91–99PubMedCrossRefGoogle Scholar
  103. Pycock CJ, Kerwin RW, Carter CJ (1980b) Effect of lesion of cortical dopamine terminals on subcortical dopamine receptors in rats. Nature 286: 74–77PubMedCrossRefGoogle Scholar
  104. Retaux S, Besson MJ, Penit-Soria J (1991) Synergism between D1 and D2 dopamine receptors in the inhibition of the evoked release of [3H]GABA in the rat prefrontal cortex. Neuroscience 43: 323–329PubMedCrossRefGoogle Scholar
  105. Roberts PJ, Anderson SD (1979) Stimulatory effect of L-glutamate and related amino acids on [3H]dopamine release from rat striatum: an in vitro model for glutamate actions. J Neurochem 32: 1539–1541PubMedCrossRefGoogle Scholar
  106. Rosin DJ, Clark WA, Goldstein M, Roth RH, Deutch AY (1992) Effects of 6hydroxydopamine lesions of the prefrontal cortex on tyrosine hydroxylase activity in subcortical dopamine systems of the rat. Neuroscience (in press)Google Scholar
  107. Sagar SM, Sharp FR, Curran T (1988) Expression of c-fos protein in brain: metabolic mapping at the cellular level. Science 240: 1328–1331PubMedCrossRefGoogle Scholar
  108. Samuel D, Errami M, Nielullon A (1990) Localization of N-methyl-D-aspartate receptors in the rat striatum: effects of specific lesions on the [3]3-(2-carboxypiperazin-4yl)propyl-1-phosphonic acid binding. J Neurochem 54: 1926–1933PubMedCrossRefGoogle Scholar
  109. Seguela P, Watkins KC, Descarries L (1988) Ultrastructural features of dopamine axon terminals in the anteromedial and the suprarhinal cortex of adult rat. Brain Res 442: 11–22PubMedCrossRefGoogle Scholar
  110. Sesack SR, Bunney BS (1989) Pharmacological characterization of the receptor mediating electrophysiological responses to dopamine in the rat medial prefrontal cortex: a microiontophoretic study. J Pharmacol Exp Ther 248: 1323–1333PubMedGoogle Scholar
  111. Sesack SR, Deutch AY, Roth RH, Bunney BS (1989) The topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study using Phaseolus vulgaris leucoagglutinin. J Comp Neurol 290: 213–242PubMedCrossRefGoogle Scholar
  112. Sheng M, Greeberg ME (1990) The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron 4: 477–485PubMedCrossRefGoogle Scholar
  113. Shepard PD, German DC (1984) A subpopulation of mesocortical dopamine neurons possess autoreceptors. Eur J Pharmacol 98: 455–456PubMedCrossRefGoogle Scholar
  114. Spencer HJ (1976) Antagonism of cortical excitation of striatal neurons by glutamic acid diethylester: evidence for glutamic acid as an excitatory transmitter in the rat striatum. Brain Res 102: 91–101PubMedCrossRefGoogle Scholar
  115. Swanson LW (1982) The projections of the ventral tegmental area and adjacent areas: a combined retrograde tracer and immunofluorescence study of the rat. Brain Res Bull 9: 321–353PubMedCrossRefGoogle Scholar
  116. Tandon R, Greden JF (1991) Negative symptoms of schizophrenia: the need for conceptual clarity. Biol Psychiatry 30: 321–325PubMedCrossRefGoogle Scholar
  117. Tassin JP, Studier JM, Herve D, Blanc G, Glowinski J (1986) Contribution of noradrenergic neurons to the regulation of dopaminergic (D1) receptor denervation supersensitivity in rat prefrontal cortex. J Neurosci 46: 243–248Google Scholar
  118. Thierry AM, Tassin JP, Blanc G, Glowinski J (1976) Selective activation of the mesocortical dopamine system by stress. Nature 263: 242–244PubMedCrossRefGoogle Scholar
  119. Thierry AM, Le Douarin C, Penit J, Ferron A, Glowinski J (1986) Variation in the ability of neuroleptics to block the inhibitory influence of dopaminergic neurons on the activity of cells in the rat prefrontal cortex. Brain Res Bull 16: 155–160PubMedCrossRefGoogle Scholar
  120. Thierry A-M, Godbut R, Mantz J, Glowinski J (1990) Influence of the ascending monoaminergic systems on the activity of the rat prefrontal cortex. In: Uylings HBM, Van Eden CG, De Bruin JPC, Corner MA, Feenstra MPG (eds) The prefrontal cortex: its structure, function, and pathology. Elsevier Science Publishers, Amsterdam, pp 377–366 (Prog Brain Res 85 )Google Scholar
  121. Vaughn C, Leff JP (1976) The influence of family and social factors on the course of psychiatric illness. Br J Psychiatry 129: 129–137CrossRefGoogle Scholar
  122. Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44: 660–669PubMedCrossRefGoogle Scholar
  123. Westerink BHC, de Vries JB (1989) On the mechanism of neuroleptic induced increase in striatal dopamine release: brain dialysis provides direct evidence for mediation by autoreceptors localized on nerve terminals. Neurosci Lett 99: 197–202PubMedCrossRefGoogle Scholar
  124. Wong M-L, Deutch AY (1991) Localization of Glu-A receptor mRNA in the sub-stantia nigra and ventral tegmental area. Soc Neurosci Abstr 17: 793Google Scholar
  125. Young AMJ, Bradford HF (1986) Excitatory amino acid neurotransmitters in the corticostriate pathway: studies using intracerebral microdialysis in vivo. J Neurochem 47: 1399–1404PubMedCrossRefGoogle Scholar
  126. Zahm DS (1991) Compartments in rat dorsal and ventral striatum revealed following injection of 6-hydroxydopamine into the ventral mesencephalon. Brain Res 552: 164–169 1991.Google Scholar
  127. Zahm DS, Heimer L (1990) Two transpallidal pathways originating in rat nucleus accumbens. J Comp Neurol 302: 437–446PubMedCrossRefGoogle Scholar
  128. Zigmond MJ, Abercrombie ED, Berger TW, Grace AA, Stricker EM (1990) Compensations after lesions of central dopaminergic neurons: some basic and clinical implications. Trends Neurosci 13: 290–295PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • A. Y. Deutch
    • 1
  1. 1.Department of Psychiatry, Connecticut Mental Health CenterYale University School of MedicineNew HavenUSA

Personalised recommendations