Neurotransmitters in the Dorsal Periaqueductal Grey and Animal Models of Panic Anxiety

  • F. G. Graeff
Chapter

Abstract

The dorsal periaqueductal grey (DPAG) of the midbrain belongs to a longitudinally organized neural system, responsible for the behavioural and neurovegetative expression of defence reactions, like fight or flight, and for the elaboration of aversive emotional/motivational states. In addition to the DPAG, the medial hypothalamus as well as the central and dorsomedial amygdala constitute the so-called ‘brain aversive system’ (for reviews see Graeff, 1987, 1988, 1990).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. American Psychiatric Association (1980). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn (DSM-III), APA Press, Washington, DC.Google Scholar
  2. American Psychiatric Association (1987). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn revised (DSM-III-R), APA Press, Washington, DC.Google Scholar
  3. Amsterdam, J. D., Berwish, N., Potter, L. and Rickeis, K. (1987). Open trial of gepirone in the treatment of major depressive disorder. Curr. Res. Clin. Exptl., 41, 185–93.Google Scholar
  4. Audi, E. A. and Graeff, F. G. (1984). Benzodiazepine receptors in the periaqueductal grey mediate anti-aversive drug action. Eur. J. Pharmacol., 103, 279–85.PubMedCrossRefGoogle Scholar
  5. Audi, E. A. and Graeff, F. G. (1987). GABAA receptors in the midbrain central grey mediate the antiaversive action of GABA. Eur. J. Pharmacol., 135, 225–9.PubMedCrossRefGoogle Scholar
  6. Audi, E. A., de Aguiar, J. C. and Graeff, F. G. (1988). Mediation by serotonin of the antiaversive effect of zimelidine and propranolol injected into the dorsal midbrain central grey. J. Psychopharmacol., 2, 26–32.PubMedCrossRefGoogle Scholar
  7. Audi, E. A., de Oliveira, C. E. and Graeff, F. G. (1989). Serotonergic mediation of the anxiolytic effect of intracerebrally injected propranolol measured in the elevated plus-maze. Braz. J. Med. Biol. Res., 22, 699–701.PubMedGoogle Scholar
  8. Bandler, R. (1984). Identification of hypothalamic and midbrain periaqueductal grey neurones mediating aggressive and defensive behaviour by intracerebral microinjections of excitatory aminoacids. In Bandler, R. (ed.), Modulation of Sensorimotor Activity during Alterations in Behavioral States, Liss, New York, 369–91.Google Scholar
  9. Beart, P. M., Nicopoulos, L. S., West, D. C. and Headley, P. M. (1988). An excitatory amino acid projection from ventromedial hypothalamus to periaqueductal gray in the rat: autogradiographic and electrophysiological evidence. Neurosci. Lett., 85, 205–11.PubMedCrossRefGoogle Scholar
  10. Blier, P., de Montigny, C. and Chaput, Y. (1987). Modifications of the serotonin system by the antidepressant treatments: implications for the therapeutic response in major depression. J. Clin. Psychopharmacol., 7, 24S–35S.Google Scholar
  11. Bovier, P., Broekkamp, C. L. E. and Lloyd, K. G. (1982). Enhancing GABAergic transmission reverses the aversive state in rats induced by electrical stimulation of the periaqueductal gray region. Brain Res., 248, 313–20.PubMedCrossRefGoogle Scholar
  12. Bovier, P., Broekkamp, C. L. E. and Lloyd, K. G. (1984). Ethyl alcohol on escape from electrical periaqueductal gray stimulation in rats. Pharmacol. Biochem. Behav., 21, 353–6.PubMedCrossRefGoogle Scholar
  13. Brandão, M. L., de Aguiar, J. C. and Graeff, F. G. (1982). GABA mediation of the anti-aversive action of minor tranquilizers. Pharmacol. Biochem. Behav., 16, 397–402.PubMedCrossRefGoogle Scholar
  14. Broekkamp, C. L. and Jenck, F. (1989). The relationship between various animal models of anxiety, fear-related psychiatric symptoms and response to serotonergic drugs. In Bevan, P., Cools, A. R. and Archer, T. (eds.), Behavioural Pharmacology of 5-HT, Erlbaum, Hillsdale, NJ, 321–35.Google Scholar
  15. Carobrez, A. B. (1987). Excitatory aminoacid mediation of the defense reaction. In Brandão, M. L. (ed.), Neurosciences and behavior, UFES-Gráfica, Vitória, Brazil, 21–9.Google Scholar
  16. Celeumans, D. L. S., Hoppenbrouwers, M. L. J. A., Gelders, Y. G. and Reyntjens, A. J. M. (1985). The influence of ritanserin, a serotonin antagonist in anxiety disorders: A double-blind placebo-controlled study versus lorazepam. Pharmacopsychiatry, 18, 303–5.CrossRefGoogle Scholar
  17. Charney, W. S., Woods, W. S., Goodman, W. K. and Henninger, G. R. (1987). Serotonin function in anxiety. II: Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects. Psychopharmacology, 92, 14–24.PubMedCrossRefGoogle Scholar
  18. Charney, D. S., Woods, S. W., Goodman, W. K., Rifkin, B., Kinch, M., Aiken, B., Quandrino, L. M. and Heninger, G. R. (1986). Drug treatment of panic disorder: The comparative efficacy of imipramine, alprazolam, and trazodone. J. Clin. Psychiat., 47, 580–6.Google Scholar
  19. Chopin, P. and Briley, M. (1987). Animal models of anxiety: the effect of compounds that modify 5-HT neurotransmission. Trends Pharmacol. Sci., 8, 383–8.CrossRefGoogle Scholar
  20. Chouinard, G., Annable, L., Fontaine, R. and Solyom, L. (1982). Alprazolam in the treatment of generalized anxiety and panic disorders: a double-blind placebo-controlled study. Psychopharmacology, 77, 229–32.PubMedCrossRefGoogle Scholar
  21. Clarke, A. and File, S. E. (1982). Effects of ACTH, benzodiazepines and 5-HT antagonists on escape from periaqueductal grey stimulation in the rat. Biol. Psychiat., 6, 27–35.Google Scholar
  22. Critcheley, M. A. E. and Handley, S. L. (1987). Effects in the X-maze anxiety model of agents acting at 5-HT1 and 5-HT2 receptors. Psychopharmacology, 93, 502–6.Google Scholar
  23. Deakin, J. K. W. (1989). 5-HT receptor subtypes in depression. In Bevan, P., Cools, A. R. and Archer, T. (eds.), Behavioral Pharmacology of 5-HT, Erlbaum, Hillsdale, NJ, 179–204.Google Scholar
  24. De Jonghe, F. (1988). Symptomatology of the depressive syndrome. In Swinkels, J. A. and Blijleven, W. (eds.), Depression, Anxiety and Aggression, Medidact, Houten, The Netherlands, 7–21.Google Scholar
  25. Den Boer, J. A. (1988). Serotonergic Mechanisms in Anxiety Disorders: an Inquiry into Serotonin Function in Panic Disorder. Cip-Gegevens Koeninglijke Bibliotheek, The Hague.Google Scholar
  26. Dunn, R. W., Corbett, R. and Fielding, S. (1989). Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze. Eur. J. Pharmacol., 169, 1–10.PubMedCrossRefGoogle Scholar
  27. Eison, A. S. and Temple, D. L. (1986). Buspirone: review of its pharmacology and current perspectives on the mechanism of action. Am. J. Med., 80, Suppl. 3B, 1–9.PubMedCrossRefGoogle Scholar
  28. Engel, J. A., Hjorth, S., Svensson, K., Carlson, A. and Liljequist, S. (1984). Anticonflict effect of the putative serotonin agonist 8-hydroxy-2-(DL-n-propylamino)-tetralin (8-OH-DPAT). Eur. J. Pharmacol., 105, 365–8.PubMedCrossRefGoogle Scholar
  29. File, S. (1987). The search for novel anxiolytics. Trends Neurosci., 10, 461–3.CrossRefGoogle Scholar
  30. Fontana, D. J. and Commissaris, R. L. (1988). Effects of acute and chronic imipramine administration on conflict behavior in the rat: a potential ‘animal model’ for the study of panic? Psychopharmacology, 95, 147–50.PubMedCrossRefGoogle Scholar
  31. Fontana, D. J., Carbary, T. J. and Commissaris, R. L. (1989). Effects of acute and chronic anti-panic drug administration on conflict behavior in the rat. Psychopharmacology, 98, 157–62.PubMedCrossRefGoogle Scholar
  32. Frazer, G. A. and Lapierre, Y. D. (1987). The effect of buspirone on panic disorder: a case report. J. Clin. Psychopharmacol., 7, 118–9.PubMedGoogle Scholar
  33. Gentil, V. (1988). The aversive system, 5-HT and panic attacks. In Simon, P., Soubrié, P. and Wiedlocher, D. (eds.), Selected Models of Anxiety, Depression and Psychosis, Karger, Basle, 142–5.Google Scholar
  34. Giral, P., Martin, P., Soubrié, P. and Simon, P. (1988). Reversal of helpless behavior in rats by putative 5-HT1A agonists. Biol. Psychiat., 23, 237–42.PubMedCrossRefGoogle Scholar
  35. Goa, K. L. and Ward, A. (1986). Buspirone: a preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic. Drug Eval., 32, 114–29.CrossRefGoogle Scholar
  36. Goldberg, H. L. and Finnerty, R. J. (1979). The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am. J. Psychiat., 136, 1184–7.PubMedCrossRefGoogle Scholar
  37. Graeff, E. O., Hunzicker, M. H. L. and Graeff, F. G. (1989). Effects of ipsapirone and BAY R 1531 on learned helplessness. Braz. J. Med. Biol. Res., 22, 1141–4.PubMedGoogle Scholar
  38. Graeff, F. G. (1987). The antiaversive action of drugs. In Thompson, T., Dews, P. B. and Barrett, J. E. (eds.), Advances in Behavioral Pharmacology, Volume 6: Neurobehavioral Pharmacology, Erlbaum, Hillsdale, NJ, 129–56.Google Scholar
  39. Graeff, F. G. (1988). Animal models of aversion. In Simon, P., Soubrié, P. and Wiedlocher, D. (eds.), Selected Models of Anxiety, Depression and Psychosis, Karger, Basle, 115–41.Google Scholar
  40. Graeff, F. G. (1990). Brain defense systems and anxiety. In Roth, M., Burrows, G. D. and Noyes, R. (eds.), Handbook of Anxiety, vol. 3, Elsevier, Amsterdam, 307–54.Google Scholar
  41. Graeff, F. G. and Schoenfeld, R. I. (1970). Tryptaminergic mechanisms in punished and nonpunished behavior. J. Pharmacol. Exp. Ther., 173, 277–83.PubMedGoogle Scholar
  42. Graeff, F. G., Carobrez, A. P. and Silveira, M. L. (1988). Excitatory amino acids and the brain aversive system. In Cavalheiro, E. A., Lehman, J. and Turski, L. (eds.), Frontiers in Excitatory Amino Acid Research, Liss, New York, 325–32.Google Scholar
  43. Gray, J. A. (1987). The Psychology of Fear and Stress, Cambridge University Press, Cambridge.Google Scholar
  44. Grunhaus, L., Gloger, S. and Weisstub, E. (1981). Panic attacks — a review of treatments and pathogenesis. J. Nerv. Ment. Dis., 169, 608–13.PubMedCrossRefGoogle Scholar
  45. Guimarães, F. S., Zuardi, A. W. and Graeff, F. G. (1987). Effect of chlorimipramine and maprotiline on experimental anxiety in humans. J. Psychopharmacol., 1, 184–92.PubMedCrossRefGoogle Scholar
  46. Haefely, W., Kyburz, E., Gerecke, M. and Mönier, H. (1985). Recent advances in the molecular pharmacology of benzodiazepine receptors and in the structure-activity relationship of their agonists and antagonists. Adv. Drug Res., 14, 165–322.Google Scholar
  47. Handley, S. L. and Mithani, S. (1984). Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of ‘fear’-motivated behavior. Naunyn-Schmiedeberg’s Arch. Pharmacol., 327, 1–5.CrossRefGoogle Scholar
  48. Hodges, H., Green, S. and Glenn, B. (1987). Evidence that the amygdala is involved in benzodiazepine and serotonergic effects on punished responding but not in discrimination. Psychopharmacology, 92, 491–504.PubMedCrossRefGoogle Scholar
  49. Hoyer, D. (1988). Functional correlates of serotonin 5-HT1 recognition sites. J. Receptor Res., 8, 59–81.Google Scholar
  50. Jacquet, Y. F. and Lajtha, A. (1974). Paradoxical effects after microinjection of morphine in the periaqueductal gray matter. Science, 185, 1055–7.PubMedCrossRefGoogle Scholar
  51. Jenck, F., Broekkamp, C. L. E. and Van Delft, A. M. L. (1989a). Effects of serotonin receptor antagonists on PAG stimulation induced aversion: different contributions of 5-HT1, 5-HT2 and 5-HT3 receptors. Psychopharmacology, 97, 489–95.PubMedCrossRefGoogle Scholar
  52. Jenck, F., Broekkamp, C. L. E. and Van Delft, A. M. L. (1989b). Opposite control mediated by central 5-HT1A and non-5-HT1A (5-HT1B or 5-HT1C) receptors on periaqueductal gray aversion. Eur. J. Pharmacol., 161, 219–21.PubMedCrossRefGoogle Scholar
  53. Jenck, F., Broekkamp, C. L. E. and Van Delft, A. M. L. (1990a). Antidepressants on aversive PAG stimulation. Eur. J. Pharmacol., in press.Google Scholar
  54. Jenck, F., Broekkamp, C. L. E. and Van Delft, A. M. L. (1990b). 5-HT1C receptors in the serotonergic control of periaqueductal gray induced aversion in rats. Psychopharmacology, 100, 372–6.PubMedCrossRefGoogle Scholar
  55. Johnston, A. L. and File, S. E. (1987). Pro-and anti-anxiety treatments and measures of anxiety in the rat. Soc. Neurosci. Abstr., 13, 452.Google Scholar
  56. Johnston, A. L. and File, S. E. (1988). Can animal tests detect panic promoting agents? Human Psychopharmacol., 3, 149–52.CrossRefGoogle Scholar
  57. Kahn, R. J., MacNair, D. M., Lipman, R. S., Covi, L., Rickels, K., Downing, R., Fisher, S. and Frankenthaler, L. M. (1986). Imipramine and chlordiazepoxide in depressive and anxiety disorders. II: Efficacy in anxious outpatients. Arch. Gen. Psychiat., 43, 79–85.PubMedCrossRefGoogle Scholar
  58. Kahn, R. S., van Praag, H. M., Wetzler, S., Asnis, G. M. and Barr, G. (1988a). Serotonin and anxiety revisited. Biol. Psychiat., 23, 189–208.PubMedCrossRefGoogle Scholar
  59. Kahn, R. S., Asnis, G. M., Wetzler, S. and van Praag, H. M. (1988b). Neuroendocrine evidence for serotonin receptor hypersensitivity in panic disorder. Psychopharmacology, 96, 360–4.PubMedCrossRefGoogle Scholar
  60. Kennett, G. A. and Curzon, G. (1989). Mechanism of action of 8-OH-DPAT on a rat model for human depression. In Bevan, P., Cools, A. R. and Archer, T. (eds), Behavioral Pharmacology of 5-HT, Erlbaum, Hillsdale, NJ, 225–9.Google Scholar
  61. Kiser, R. S. Jr and Lebovitz, R. M. (1975). Monoaminergic mechanisms in aversive brain stimulation. Physiol. Behav., 15, 47–53.PubMedCrossRefGoogle Scholar
  62. Klein, D. F. (1964). Delineation of two drug responsive anxiety syndromes. Psychopharmacology, 5, 397–408.CrossRefGoogle Scholar
  63. Krieger, J. E. and Graeff, F. G. (1985). Defensive behavior and hypertension induced by glutamate in the midbrain central gray of the rat. Braz. J. Med. Biol. Res., 18, 61–7.PubMedGoogle Scholar
  64. Liebowitz, M. R. (1989). Antidepressants in panic disorders. Brit. J. Psychiat., 155 (suppl. 6), 46–52.Google Scholar
  65. Marks, I. (1987). Agoraphobia, panic disorder and related conditions in the DSM-IIIR and ICD-10. J. Psychopharmacol., 1, 6–12.PubMedCrossRefGoogle Scholar
  66. Martin, P., Laporte, A. M., Soubrié, P., El Mestikawy, S. and Hamon, M. (1989). Reversal of helpless behaviour in rats by serotonin uptake inhibitors. In Bevan, P., Cools, A. R. and Archer, T. (eds.), Behavioral Pharmacology of 5-HT, Erlbaum, Hillsdale, NJ, 231–3.Google Scholar
  67. Mavissakalian, M. (1988). Comments on the diagnosis and treatment of anxiety disorders. In Swinkels, J. A. and Blijleven, W. (eds), Depression, Anxiety and Aggression, Medidact, Houten, The Netherlands, 85–90.Google Scholar
  68. Middlemiss, D. N. (1984). Stereoselective blockade at [3H] 5-HT binding sites and at the 5-HT autoreceptor by propranolol. Eur. J. Pharmacol., 101, 289–93.PubMedCrossRefGoogle Scholar
  69. Moser, P. (1989). An evaluation of the elevated plus-maze test using the novel anxiolytic buspirone. Psychopharmacology, 99, 48–53.PubMedCrossRefGoogle Scholar
  70. Murphy, D. L., Siever, L. J. and Insel, T. R. (1985). Therapeutic responses to tricyclic antidepressants and related drugs in non-affective disorder patient populations. Prog. Neuro-Psychopharmacol. Biol. Psychiat., 9, 3–13.CrossRefGoogle Scholar
  71. Nashold, B. S. Jr, Wilson, N. P. and Slaughter, G. S. (1969). Sensations evoked by stimulation in the midbrain of man. J. Neurosug., 30, 14–24.CrossRefGoogle Scholar
  72. Nashold, B. S. Jr, Wilson, N. P. and Slaughter, G. S. (1974). The midbrain and pain. In Bonica, J.J. (ed.), Advances in Neurology, vol. 4: International Symposium on Pain, Raven, New York, 191–6.Google Scholar
  73. Nieuwenhuys, R. (1985). Chemoarchitecture of the Brain. Springer, Berlin.CrossRefGoogle Scholar
  74. Noyes, R., Anderson, D. J., Clancy, J., Crowe, R. R., Slymen, D. J., Ghoneim, M. M. and Hinrichs, J. V. (1984). Diazepam and propranolol in panic disorder and agoraphobia. Arch. Gen. Psychiat., 41, 287–92.PubMedCrossRefGoogle Scholar
  75. Panksepp, J. (1982). Toward a general psychobiological theory of emotions. Behav. Brain Sci., 5, 407–67.CrossRefGoogle Scholar
  76. Pellow, S. and File, S.E. (1986). Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol. Biochem. Behav., 24, 525–9.PubMedCrossRefGoogle Scholar
  77. Pellow, S., Johnston, A. L. and File, S. E. (1987). Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat. J. Pharm. Pharmacol., 39, 917–28.PubMedCrossRefGoogle Scholar
  78. Pellow, S., Chopin, P., File, S. E. and Briley, M. (1985). Validation of open: closed arm entries in the elevated plus-maze as a measure of anxiety in the rat. J. Neurosci. Meth., 14, 149–67.CrossRefGoogle Scholar
  79. Schatzberg, A. F. and Cole, J. (1978). Benzodiazepines in depressive disorders. Arch. Gen. Psychiat., 35, 1359–65.PubMedCrossRefGoogle Scholar
  80. Schenberg, L. C. and Graeff, F. G. (1978). Role of the periaqueductal gray substance in the antianxiety action of benzodiazepines. Pharmacol. Biochem. Behav., 9, 287–95.PubMedCrossRefGoogle Scholar
  81. Schmitt, P., Di Scala, G., Brandão, M. L. and Karli, P. (1984). Periventricular structures, elaboration of aversive effects and processing of sensory information. In Bandler, R. (ed.), Modulation of Sensorimotor Activity during Alterations in Behavioral States, Liss, New York, 393–414.Google Scholar
  82. Schütz, M. T. B., de Aguiar, J. C. and Graeff, F. G. (1985). Antiaversive role of serotonin on the dorsal periaqueductal grey matter. Psychopharmacology, 85, 340–5.PubMedCrossRefGoogle Scholar
  83. Schweitzer, E. E., Amsterdam, J., Rickels, K., Kaplan, M. and Droba, M. (1986). Open trial of buspirone in the treatment of major depressive disorder. Psychopharmacol. Bull., 22, 183–5.Google Scholar
  84. Scott Young, W. and Kuhar, M. J. (1980). Radiohistochemical localization of benzodiazepine receptors in the rat brain. J. Pharmacol Exp. Ther., 212, 337–46.Google Scholar
  85. Sheehan, D. V. (1982). Panic attacks and phobias. N. Engl. J. Med., 307, 156–8.PubMedCrossRefGoogle Scholar
  86. Sheehan, D. V., Raj, A. B., Harnett-Sheehan, K. and Soto, S. (1988). The relative efficacy of buspirone, imipramine and placebo in panic disorder: a preliminary report. Pharmacol Biochem. Behav., 29, 815–7.PubMedCrossRefGoogle Scholar
  87. Sheehan, D. V., Davidson, J., Manschreck, T., Van Wyck Fleet, J. (1983). Lack of efficacy of a new antidepressant (bupropion) in the treatment of panic disorders with phobias. J. Clin. Psychopharmacol., 3, 28–31.PubMedCrossRefGoogle Scholar
  88. Shepherd, J. K. and Rodgers, R. J. (1989). Acute and chronic effects of the triazolobenzodiazepine, alprazolam, on defeat and analgesia evoked by conspecific attack in male mice. Behav. Pharmacol., 1, 75–83.PubMedCrossRefGoogle Scholar
  89. Soubrié, P. (1986). Reconciling the role of central serotonin neurons in human and animal behavior. Behav. Brain Sci., 9, 319–64.CrossRefGoogle Scholar
  90. Soubrié, P. (1989). 5-HT1A receptors: a bridge between anxiety and depression? In Bevan, P., Cools, A. R. and Archer, T. (eds.), Behav. Pharmacol., of 5-HT, Erlbaum, Hillsdale, NJ, 337–52.Google Scholar
  91. Spier, S. A., Rosenbaum, J. F. and Woods, S. W. (1986). Treatment of panic disorder and agoraphobia with clonazepam. J. Clin. Psychiat., 47, 238–42.Google Scholar
  92. Stein, L., Wise, C. D. and Berger, B. D. (1973). Antianxiety action of benzodiazepines: decrease in activity of serotonin neurons in the punishment system. In Garattini, S., Mussini, E. and Randall, L. O. (eds.), Benzodiazepines, Raven, New York, 299–326.Google Scholar
  93. Stephens, D. N. and Andrews, J. S. (1988). N-methyl-D-aspartate antagonists in animal models of anxiety. In Cavalheiro, E. A., Lehman, J. and Turski, L. (eds.), Frontiers in Excitatory Amino Acid Research, Liss, New York, 309–16.Google Scholar
  94. Teicher, M. H. (1988). Biology of anxiety. Med. Clin. North America, 72, 791–814.Google Scholar
  95. Tiller, J., Schweitzer, I., Macquire, K. and Davies, B. (1989). Is diazepam an antidepressant? Brit. J. Psychiat., 155, 483–9.PubMedCrossRefGoogle Scholar
  96. Traber, J. and Glaser, T. (1987). 5-HT receptor-related anxiolytics. Trends Pharmacol. Sci., 8, 432–7.CrossRefGoogle Scholar
  97. Treit, D. (1985). Animal models for the study of anti-anxiety agents: a review. Neurosci. Biobehav. Rev., 9, 203–22.PubMedCrossRefGoogle Scholar
  98. Tyrer, P. (1986). Classification of anxiety disorders: a critique of DSM-III. J. Affect. Disorders, 11, 99–104.PubMedCrossRefGoogle Scholar
  99. Tyrer, P. (1988). Current status of β-blocking drugs in the treatment of anxiety disorders. Drugs, 36, 773–83.PubMedCrossRefGoogle Scholar
  100. Watkins, J. C. (1986). Selective antagonists define sub-classes of excitatory amino acid receptors. In Iversen, L. L. and Goodman, E. C. (eds.), Fast and Slow Chemical Signalling in the Nervous System, Oxford University Press, Oxford, 89–105.Google Scholar
  101. Willner, P. (1985). Antidepressants and serotonergic neurotransmission: an integrative review. Psychopharmacology, 85, 387–404.PubMedCrossRefGoogle Scholar

Copyright information

© Macmillan Publishers Limited 1991

Authors and Affiliations

  • F. G. Graeff
    • 1
  1. 1.Laboratory of Psychobiology FFCLRPCampus of the University of São PauloBrazil

Personalised recommendations