Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Antidepressants and serotonergic neurotransmission: An integrative review


The effects of acute and chronic antidepressant treatment on various aspects of 5-HT neurotransmission are reviewed, in order to assess the net effect of antidepressants on transmission across 5-HT synapses. Events considered include presynaptic effects of antidepressants (on autoreceptor function, uptake and turnover) and effects on postsynaptic receptor function (assessed by electrophysiological, neuroendocrine, behavioural, and receptor binding methods). Acute antidepressant treatment has variable effects: transmission may be enhanced, unchanged or reduced, depending mainly upon the relative contributions of 5-HT uptake blockade and 5-HT receptor antagonism. However, on chronic administration, most antidepressants appear to enhance 5-HT transmission. This effect is clearest in the case of ECS, which has little effect on 5-HT turnover, but reduces uptake and increases postsynaptic receptor function. MAOIs may be an exception: there is little evidence that MAOIs enhance 5-HT transmission following chronic treatment. Most other anti-depressant drugs, including some which are powerful receptor antagonists on acute administration, reduce 5-HT receptor function briefly, but enhance receptor function if several hours elapse between the final injection and testing. Zimelidine has little effect on postsynaptic receptor function, but enhances 5-HT transmission by its powerful blockade of 5-HT uptake. Chronic treatment with antidepressant drugs has usually been found to reduce binding to 5-HT2 receptors; it is difficult to reconcile these observations with the functional studies. In general, with the possible exception of MAOIs, chronic administration of antidepressants may enhance 5-HT transmission by both pre- and post-synaptic effects, and the relative contributions vary. This conclusion supports the classical “indoleamine hypothesis of depression” rather than the more recent “hypersensitive serotonin receptor” theory.

This is a preview of subscription content, log in to check access.


  1. Abrams R, Essman WB, Taylor MA, Fink F (1976) Concentration of 5-hydroxyindoleacetic acid, homovanillic acid and tryptophan in the cerebrospinal fluid of depressed patients before and after ECT. Biol Psychiatr 11:85–90

  2. Alpers HS, Himwich HE (1972) The effects of chronic imipramine administration on rat brain levels of serotonin, 5-hydroxyindoleacetic acid, norepinephrine and dopamine. J Pharmacol Exp Ther 180:531–538

  3. Amin MM, Ananth JV, Coleman BS, Darcourt G, Farkas T, Goldstein B, Lapierre YD, Paykel E, Wakelin JS (1984) Fluvoxamine: Antidepressant effects confirmed in a placebo-controlled study. Clin Neuropharmacol (Suppl 1) 7:580–581

  4. Aprison MH, Takahashi R, Tachiki K (1978) Hypersensitive serotonergic receptors involved in clinical depression — a theory. In: Haber B, Aprison MH (eds) Neuropharmacology and behaviour. Plenum Press, New York, pp 23–53

  5. Aprison MH, Hintgen JN, Nagayama H (1982) Testing a new theory of depression with an animal model: Neurochemical-behavioural evidence for postsynaptic serotonergic receptor involvement. In: Langer SZ, Takahashi R, Segawa T, Briley M (eds) New vistas in depression. Pergamon Press, New York, pp 171–178

  6. Asberg M, Bertilsson L, Tuck D, Cronholm B, Sjoqvist F (1973) Indoleamine metabolites in the cerebrospinal fluid of depressed patients before and during treatment with nortriptyline. Clin Pharmacol Ther 14:227–286

  7. Asberg M, Ringberger VA, Sjoqvist F, Thoren P, Traskman L, Tuck RJ (1975) Monoamine metabolites in cerebrospinal fluid and serotonin uptake inhibition during treatment with chlorimipramine. Clin Pharmacol Ther 21:201–207

  8. Ashcroft GW, Crawford TBB, Eccleston D, Sharman DF, McDougall EJ, Stanton JB, Binns JK (1966) 5-hydroxyindole compounds in the cerebrospinal fluid of patients with psychiatric or neurological disease. Lancet 2:1049–1052

  9. Atterwill CK (1980) Lack of effect of repeated electroconvulsive shock on 3H-spiroperidol and 3H-5-HT binding and cholinergic parameters in rat brain. J Neurochem 35:729–734

  10. Balldin J, Bolle P, Eden S, Eriksson E, Modigh K (1980) Effects of electroconvulsive treatment on growth hormone secretion induced by monoamine receptor agonists in reserpine-pretreated rats. Psychoneuroendocrinology 5:329–337

  11. Ban TA (1969) The use of amphetamines in adult psychiatry. Semin Psychiatr 1:129–143

  12. Barbaccia ML, Brunello N, Chuang DM, Costa E (1983) On the mode of action of imipramine: Relationship between serotonergic axon terminal function and down-regulation of beta-adrenergic receptors. Neuropharmacology 22:373–383

  13. Bech P (1984) Citalopram versus clomipramine: A controlled clinical study. Clin Neuropharmacol (Suppl 1) 7:876–877

  14. Bennett JP, Aghajanian GK (1974) d-LSD binding to brain homogenates: Possible relationship to serotonin receptors. Life Sci 15:1935–1944

  15. Bennett JP, Snyder SH (1976) Serotonin and lysergic acid diethylamide binding in rat brain membranes: relationship to postsynaptic serotonin receptors. Mol Pharmacol 12:373–389

  16. Bergstrom DA, Kellar KJ (1979a) Effect of electroconvulsive shock on monoaminergic receptor binding sites in rat brain. Nature 278:464–466

  17. Bergstrom DA, Kellar KJ (1979b) Adrenergic and serotonergic receptor binding in rat brain after chronic desmethylimipramine treatment. J Pharmacol Exp Ther 209:256–261

  18. Bertilsson L, Asberg M, Thoren P (1976) Differential effect of chlorimipramine and nortriptyline on cerebrospinal fluid metabolites of serotonin and noradrenaline in depression. Eur J Clin Pharmacol 21:194–200

  19. Bhavsar VH, Dhumal VR, Kelkar VV (1981) The effect of some anti-epilepsy drugs on enhancement of the monoamine-mediated behavioural responses following the administration of electroconvulsive shocks to rats. Eur J Pharmacol 74:243–247

  20. Bhavsar VH, Dhumal VR, Kelkar VV (1983) The effect of estradiol on the alterations in monoamine-mediated behavioural responses induced by administration of electroconvulsive shocks or imipramine to female rats. Neuropharmacology 22:751–756

  21. Bjerkenstedt L, Edman G, Flyckt L, Sedvall G, Wiesel F (1984) Clinical and biochemical effects of citalopram in depressed patients. Clinical Psychopharmacol (Suppl 1) 7:874–875

  22. Blackburn TP, Foster GA, Greenwood DT, Howe R (1978) Effects of viloxazine, its optical isomers and its major metabolites on biogenic amine uptake mechanisms in vitro and in vivo. Eur J Pharmacol 52:367–374

  23. Blackshear MA, Sanders-Bush E (1982) Serotonin receptor sensitivity after acute and chronic treatment with mianserin. J Pharmacol Exp Ther 221:303–308

  24. Blier P, De Montigny C (1980) Effect of chronic tricyclic antidepressant treatment on the serotonergic autoreceptor: A microiontophoretic study in the rat. Naunyn Schmiedebergs Arch Pharmacol 314:123–128

  25. Blier P, De Montigny C (1983) Electrophysiological investigations on the effect of repeated zimelidine administration on serotonergic neurotransmission in the rat. J Neurosci 3:1270–1278

  26. Blier P, De Montigny C (1984a) The effect of repeated administration of monoamine oxidase inhibitors on the firing activity of serotonergic and noradrenergic neurons. Abstr. 14th CINP, Florence, p 38

  27. Blier P, De Montigny C (1984b) Enhancement of serotonergic neurotransmission by non-tricyclic antidepressant drugs: Single cell studies in the rat. Abstr. 14th CINP, Florence, p 829

  28. Born GVR, Grignani G, Martin K (1980) Long-term effect of lithium on the uptake of 5-hydroxytryptamine by human platelets. Br J Clin Pharmacol 9:321–325

  29. Bowers MB (1974) Amitriptyline in man: decreased formation of central 5-hydroxyindoleacetic acid. Clin Pharmacol Ther 15:167–170

  30. Bowers MB, Heninger GR, Gerbode F (1969) Cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in psychiatric patients. Int J Neuropharmacol 8:255–262

  31. Bradshaw CM, Roberts MHT, Szabadi E (1974) Effects of imipramine and desipramine on responses of single cortical neurones to noradrenaline and 5-hydroxytryptamine. Br J Pharmacol 52:349–358

  32. Briley M, Raisman R, Arbilla S, Casadamont M, Langer SZ (1982) Concomitant decrease in 3H-imipramine binding in cat brain and platelets after chronic treatment with imipramine. Eur J Pharmacol 81:309–314

  33. Buus Lassen J (1978) Potent and long-lasting potentiation of two 5-hydroxytryptophan-induced effects in mice by three selective 5-HT uptake inhibitors. Eur J Pharmacol 47:351–358

  34. Cairncross KD, Cox B, Forster C, Wren AF (1978) A new model for the detection of antidepressant drugs: Olfactory bulbectomy in the rat compared with existing models. J Pharmacol Meth 1:131–143

  35. Cairncross KD, Cox B, Forster C, Wren AF (1979) Olfactory projection systems, drugs and behaviour: A review. Psychoneuroendocrinology 4:253–272

  36. Campbell IC, Marshall EF (1974) Effects of chronic regimens of phenelzine, tranylcypromine, and imipramine on rat brain norepinephrine and serotonin. J Pharmacol (Suppl 2) 5:14

  37. Campbell IC, Robinson DS, Lovenberg W, Murphy DL (1979) The effects of chronic regimens of clorgyline and pargyline on monoamine metabolism in the rat brain. J Neurochem 32:49–55

  38. Carlsson A, Lindqvist M (1978) Effects of antidepressant agents on the synthesis of brain monoamines. J Neur Transm 43:73–91

  39. Carlsson A, Corrodi H, Fuxe K, Hokfelt T (1969) Effect of antidepressant drugs on the depletion on intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-alpha-ethyl-meta-tyramine. Eur J Pharmacol 5:357–366

  40. Carter RB, Appel JB (1976) Blockade of the behavioural effects of 5-HTP by the decarboxylase inhibitor Ro4-4602. Pharmacol Biochem Behav 4:407–409

  41. Carter RB, Dykstra LA, Leander JD, Appel JB (1978) Role of peripheral mechanism in the behavioural effects of 5-hydroxytryptophan. Pharmacol Biochem Behav 9:249–253

  42. Charney DS, Heninger GR (1983) Monoamine receptor sensitivity and depression: Clinical studies of antidepressant effects on serotonin and noradrenergic function. Psychopharmacol Bull 19:490–495

  43. Charney DS, Menkes DB, Heninger GR (1981) Receptor sensitivity and the mechanism of action of antidepressant treatment: Implications for the etiology and treatment of depression. Arch Gen Psychiatry 38:1160–1180

  44. Charney DS, Heninger GR, Reinhard JF, Sternberg D, Hafstad K (1982) The effect of intravenous L-tryptophan on prolactin and growth hormone and mood in healthy subjects. Psychopharmacology 77:217–222

  45. Claghorn J, Gershon S, Goldstein BJ, Behrnetz S, Bush DF, Huitfeldt B (1983) A double-blind evaluation of zimelidine in comparison to placebo and amitriptyline in patients with major depressive disorder. Prog Neuropsychopharmacol 7:367–382

  46. Cooper DS, Gelenburg AJ, Wojcik JC, Saxe V, Ridgway EC, Maloof F (1981) The effect of amoxapine and imipramine on serum prolactin levels. Arch Int Med 141:1023–1025

  47. Coppen A, Wood KM (1980) Peripheral serotonergic and adrenergic responses in depression. Acta Psychiatr Scand (Suppl 61) 280:21–28

  48. Coppen A, Rao VAR, Bishop M, Abou-Saleh MT, Wood K (1980) Neuroendocrine studies in affective disorders. I. Plasma prolactin response to thyrotropin-releasing hormone in affective disorders: Effect of ECT. J affect Dis 2:311–315

  49. Coppen A, Swade C, Wood K (1981) The action of antidepressant drugs on 5-hydroxytryptamine uptake by platelets—relationship to therapeutic effect. Acta Psychiat Scand (Suppl 63) 290:236–243

  50. Corrodi H, Fuxe K (1969) Decreased turnover in central 5-HT nerve terminals induced by antidepressant drugs of the imipramine typ. Eur J Pharmacol 7:76–59

  51. Costain DW, Green AR, Grahame-Smith DG (1979) Enhanced 5-hydroxytryptamine-mediated behavioural responses in rats following repeated electroconvulsive shock: relevance to the mechanism of the antidepressive effect of electroconvulsive therapy. Psychopharmacology 61:167–170

  52. Cowen PJ, Grahame-Smith DG, Green AR, Heal DJ (1982) beta-adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses. Br J Pharmacol 76:265–270

  53. Dahl L-E, Lundin L, Honore PleF, Dencker SJ (1982) Antidepressant effect of femoxetine and desipramine and relationship to the concentration of amine metabolites in cerebrospinal fluid: A double-blind evaluation. Acta Psychiatr Scand 66:9–17

  54. De Montigny C (1981) Enhancement of the 5-HT neurotransmission by antidepressant treatments. J Physiol (Paris) 77:455–461

  55. De Montigny C, Aghajanian GK (1978) Tricyclic antidepressants: Long-term treatment increases responsivity of rat forebrain neurons to serotonin. Science 202:1303–1306

  56. De Montigny C, Blier P, Caille G, Kouassi E (1981a) Pre- and postsynaptic effects of zimelidine and norzimelidine on the serotonergic system: Single cell studies in the rat. Acta Psychiatr Scand (Suppl 63) 290:79–90

  57. De Montigny C, Tan A-T, Caille G (1981b) Short-term lithium enhances 5-HT neurotransmission in rats administered chronic antidepressant treatments. Soc Neurosci Abstr 7:646

  58. Deakin JFW, Owen F, Cross AJ, Dashwood MJ (1981) Studies on possible mechanism of action of electroconvulsive therapy: Effects of repeated electrically induced seizures on rat brain receptors for monoamines and other neurotransmitters. Psychopharmacology 73:345–349

  59. Dickinson SL, Curzon G (1983) Roles of dopamine and 5-hydroxytryptamine in stereotyped and non-stereotyped behaviour. Neuropharmacology 22:805–812

  60. Drust EG, Sloviter RS, Connor JD (1979) Effect of morphine on “wet-dog” shakes caused by cerebroventricular injections of serotonin. Pharmacology 18:299–305

  61. Dumbrille-Ross A, Tang SW, Coscina DV (1982) Lack of effect of Raphe lesions on serotonin S2 receptor changes induced by amitriptyline and desmethylimipramine. Psychiatr Res 7:145–151

  62. Ebert MH, Baldessarini RJ, Lipinski JF, Berv K (1973) Effects of electroconvulsive seizures on amine metabolism in the rat brain. Arch Gen Psychiatry 29:297–401

  63. Engel J, Hanson LCF, Roos B-E (1981) Effect of electroshock on 5-HT metabolism in rat brain. Psychopharmacology 20:197–200

  64. Ettigi PG, Brown GM (1977) Psychoneuroendocrinology of affective disorder: An overview. Am J Psychiatry 134:493–501

  65. Evans JPM, Grahame-Smith DG, Green AR, Tordoff AFC (1976) Electroconvulsive shock increases the behavioural responses of rats to brain 5-hydroxytryptamine accumulation and central nervous system stimulant drugs. Br J Pharmacol 56:193–199

  66. Feldmann HS, Denber HCB (1982) Long-term study of fluvoxamine: A new rapid-acting antidepressant. Int Pharmacopsychiatr 17:114–122

  67. Fillion G, Beaudoin D, Rousselle JC, Deniau JC, Fillion MP, Dray F, Jacob J (1979) Decrease of 3H-5-HT high affinity binding and 5-HT adenylate cyclase activation after kainic acid lesions in rat brain striatum. J Neurochem 33:567–570

  68. Fillion G, Fillion MP, Rouselle JC (1981) Augmentation de l'affinité du recepteur 5-HT et diminution de l'activité adenylate cyclase sensible à la 5-HT par exposition prolongée à la 5-HT. J Physiol (Paris) 77:363–368

  69. Finberg JPM, Youdim MBH (1983) Selective MAO A and B inhibitors: Their mechanism of action and pharmacology. Neuropharmacology 22:441–446

  70. Flor-Henry P (1979) On certain aspects of the localization of the cerebral systems regulating and determining emotion. Biol Psychiatry 14:677–698

  71. Friedman E, Dallob A (1979) Enhanced serotonin receptor activity after chronic treatment with imipramine or amitriptyline. Commun Psychopharm 3:89–92

  72. Friedman E, Dallob A, Levine G (1979) The effect of long-term lithium treatment on reserpine-induced supersensitivity in dopaminergic and serotonergic transmission. Life Sci 25:1263–1266

  73. Fuxe K, Ogren S-O, Agnati LF (1979) The effects of chronic treatment with the 5-hydroxytryptamine uptake blocker zimelidine on central 5-hydroxytryptamine mechanism. Evidence for the induction of a low affinity binding site for 5-hydroxytryptamine. Neurosci Lett 14:307–312

  74. Fuxe K, Ogren S-O, Agnati LF, Eneroth P, Holm AC, Andersson K (1981) Long-term treatment with zimelidine leads to a reduction in 5-hydroxytryptamine neurotransmission within the central nervous system of the mouse and rat. Neurosci Lett 21:57–62

  75. Fuxe K, Ogren S-O, Agnati LF, Andersson K, Eneroth P (1982a) Effects of subchronic antidepressant drug treatment on central serotonergic mechanisms in the male rat. In: Costa E, Racagni G (eds) Typical and atypical antidepressants: Molecular mechanisms. Raven Press, New York, pp 91–107

  76. Fuxe K, Ogren S-O, Andersson K, Eneroth P, Agnati LF (1982b) The effects of subchronic antidepressant drug treatment on the secretion of adenohypophyseal hormones and of corticosterone in the male rat. In: Costa E, Racagni G (eds) Typical and atypical antidepressants: Molecular mechanisms. Raven Press, New York, pp 109–120

  77. Fuxe K, Ogren S-O, Agnati LF, Andersson K, Eneroth P (1982c) On the mechanism of action of antidepressant drugs: Indications of reductions in 5-HT neurotransmission in some brain regions upon subchronic treatment. In: Langer SZ, Takahashi R, Segawa T, Briley M (eds) New vistas in depression. Pergamon Press, New York, pp 49–63

  78. Fuxe K, Ogren S-O, Agnati LF, Benfenati F, Fredholm B, Andersson K, Zini I, Eneroth P (1983) Chronic antidepressant treatment and central 5-HT synapses. Neuropharmacology 22:389–400

  79. Gallager DW, Bunney WE (1979) Failure of chronic lithium treatment to block tricyclic antidepressant-induced 5-HT supersensitivity. Naunyn-Schmiedebergs Arch Pharmacol 307:129–133

  80. Geller I (1973) Effects of para-chlorophenylalanine and 5-hydroxytryptophan on alcohol intake in the rat. Pharmacol Biochem Behav 1:361–365

  81. Gerbino L, Olesahnsky M, Gershon S (1978) Clinical use and mode of action of lithium. In: Lipton MA, DiMaschio A, Killam KF (eds) Psychopharmacology: A generation of progress. Raven Press, New York, pp 1261–1275

  82. Ghose K, Gupta R, Coppen A, Lund J (1977) Antidepressant evaluation and the pharmacological actions of FG 4963 in depressive patients. Eur J Clin Pharmacol 42:31–37

  83. Gillin JC (1983) The sleep therapies of depression. Prog Neuropsychopharmacology 7:351–364

  84. Giret M, Launay JM, Dreux C, Zarifian E, Benyacoub K, Loo H (1980) Modifications of biochemical parameters in blood platelets of schizophrenic and depressive patients. Neuropsychobiology 6:290–296

  85. Gold R, Morgenstern R, Fink H (1980) Effects of atypical antidepressants on LSD potentiated apomorphine hypermotility in rats. Acta Biol Med Ger 39:917–921

  86. Gram LF (1984) Clinical studies with femoxetine: A critical review. Clin Neuropharmacol (Suppl 1) 7:872–873

  87. Green AR, Deakin JFW (1980) Brain noradrenaline depletion prevents ECS-induced enhancement of serotonin- and dopamine-mediated behaviour. Nature 285:232–233

  88. Green AR, Heal DJ, Grahame-Smith DG (1977a) Further observations on the effect of repeated electroconvulsive shock on the behavioural responses of rat produced by increases in the functional activity of 5-hydroxytryptamine and dopamine. Psychopharmacology 52:195–200

  89. Green AR, Mitchell BD, Tordoff AFC, Youdim MBH (1977b) Evidence for dopamine deamination by both type A and type B monoamine oxidase in rat brain in vivo and for the degree of inhibition of enzyme necessary for increased functional activity of dopamine and 5-hydroxytryptamine. Br J Pharmacol 60:343–349

  90. Green AR, Costain DW, Deakin JWF (1980) Enhanced 5-hydroxytryptamine and dopamine-mediated behavioural responses following convulsions. III. The effects of monoamine antagonists and synthesis inhibitors on the ability of electroconvulsive shock to enhance responses. Neuropharmacology 19:907–914

  91. Green AR, Heal DJ, Johnson P, Laurence BE, Nimgaonkar VL (1983b) Antidepressant treatments: effects in rodents on dose-response curves of 5-hydroxytryptamine- and dopamine-mediated behaviours and 5-HT2 receptor number in frontal cortex. Br J Pharmacol 80:377–385

  92. Green AR, Johnson P, Nimgaonkar VL (1983a) Increased 5-HT2 receptor number in brain as a probable explanation for the enhanced 5-hydroxytryptamine-mediated behaviour following repeated electroconvulsive shock administration to rats. Br J Pharmacol 80:173–177

  93. Haigler HJ, Aghajanian GK (1974) Lysergic acid diethylamide and serotonin: A comparison of effects on serotonin neurons and neurons receiving a serotonergic input. J Pharmacol Exp Ther 188:688–699

  94. Hall H, Ross SB, Ogren S-O (1982) Effects of zimelidine on various transmitter systems in the brain. In: Costa E, Racagni G (eds) Typical and atypical antidepressants: Molecular mechanisms. Raven Press, New York, pp 321–325

  95. Heel RC, Morley PA, Brogden RN, Carmine AA, Speight TM, Avery GS (1982) Zimelidine: A review of its pharmacological properties and therapeutic efficacy in depressive illness. Drugs 24:169–206

  96. Hill SY (1974) Intraventricular injection of 5-hydroxytryptamine and alcohol consumption in rats. Biol Psychiatry 8:151–158

  97. Hwang EC, Van Woert MH (1980) Acute versus chronic effects of serotonin uptake blockers on potentiation of the “serotonin syndrome”. Commun Psychopharmacology 4:161–167

  98. Hytell J, Overo KF, Arnt J (1984) Biochemical effects and drug levels in rats after long-term treatment with the specific 5-HT uptake inhibitor citalopram. Psychopharmacology 83:20–27

  99. Jones RSG (1980) Enhancement of 5-hydroxytryptamine-induced behavioural effects following chronic administration of antidepressant drugs. Psychopharmacology 69:307–311

  100. Kaplan RD, Mann JJ (1982) Altered platelet serotonin uptake kinetics in schizophrenia and depression. Life Sci. 31:583–588

  101. Kellar KJ, Bergstrom DA (1983) Electroconvulsive shock: Effects on biochemical correlates of neurotransmitter receptors in rat brain. Neuropharmacology 22:401–406

  102. Kellar KJ, Cascio CS, Butler JA, Kurtzke RN (1981) Differential effects of electroconvulsive shock and antidepressant drugs on serotonin-2 receptors in rat brain. Eur J Pharmacol 69:515–518

  103. Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522

  104. Kendall DA, Duman R, Slopis J, Enna SJ (1982) Influence of adrenocroticotropin hormone and yohimbine on anti-depressant-induced declines in rat brain neurotransmitter receptor binding and function. J Pharmacol Exp Ther 22:566–571

  105. Kinnier WJ, Chuang DM, Costa E (1980) Down regulation of dihydroalprenolol and imipramine binding sites in brain of rats repeatedly treated with imipramine. Eur J Pharmacol 67:289–294

  106. Koide T, Matsushita H (1981) Influence of a chronic new potential antidepressant, 1-[3-(dimethylamino)propyl]-5-methyl-3-phenyl-1H-indazole (FS32) and its N-desmethylated compound (FS97) treatment on monoaminergic receptor sensitivity in the rat brain. Neuropharmacology 20:285–292

  107. Lahti RA, Barsuhn C (1980) The effect of antidepressants on L-5HTP-induced changes in rat plasma corticosteroids. Res Commun Chem Pathol Pharmacol 28:343–349

  108. Lai JCK, Leung TKC, Guest JF, Lim L, Davison AN (1980) The monoamine oxidase inhibitors clorgyline and L-deprenyl also affect the uptake of dopamine, noradrenaline and serotonin by rat brain synaptosomal preparations. Biochem Pharmacol 29:2763–2767

  109. Langer SZ, Raisman R (1983) Binding of [3H]imipramine and [3H]desipramine as biochemical tools for studies in depression. Neuropharmacology 22:407–413

  110. Langer SZ, Briley MS, Raisman R, Henry J-F, Morselli PL (1980) Specific 3H-imipramine binding in human platelets: influence of age and sex. Naunyn-Schmiedebergs Arch Pharmacol 313:189–194

  111. Langer SZ, Zarifian E, Briley M, Raisman R, Sechter D (1981) High affinity binding of 3H-imipramine in brain and platelets and its relevance to the biochemistry of affective disorders. Life Sci 29:211–220

  112. Lebrecht V, Nowak JZ (1980) Effect of single and repeated electroconvulsive shock on serotonergic system in rat brain. II. Behavioural studies. Neuropharmacology 19:1055–1061

  113. Lecrubier Y, Puech AJ, Jouvent R, Simon P, Widlocher D (1980) A beta adrenergic stimulant (salbutamol) versus imipramine in depression: A controlled study. Br J Psychiatry 136:354–358

  114. Lemberger L, Bergstrom R, Aronoff G, Farid N, Wolen R (1984) Specific serotonin uptake blockers: Clinical pharmacology and antidepressant action. Clin Neuropharmacol (Suppl 1) 7:324–325

  115. Leonard BE (1982) On the mode of action of mianserin. In: Costa E, Racagni G (eds) Typical and atypical antidepressants: molecular mechanisms. Raven Press, New York, pp 301–319

  116. Leonard BE, kafoe WF (1979) A comparison of the acute and chronic effects of four antidepressant drugs on the turnover of serotonin, dopamine and noradrenaline in the rat brain. Biochem Pharmacol 25:1939–1942

  117. Leysen J (1984) Problems in in vitro receptor binding studies and identification and role of serotonin receptor sites. Neuropharmacology 23:247–254

  118. Leysen JE, Niemegeers CJE, Tollenaere JP, Laduron PM (1978) Serotonergic component of neuroleptic receptors. Nature 272:163–166

  119. Leysen JE, Awouters F, Kennis L, Laduron PM, Vendenberk J, Janssen PAJ (1981) Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci 28:1015–1022

  120. Leysen JE, Niemegeers CJE, Van Nueten JM, Laduron PM (1982) [3H]Ketanserin (R 41 468), a selective 3H-ligand for serotonin-2 receptor binding sites. J Mol Pharmacol 21:301–314

  121. Leysen JE, Van Gompel P, Verwimp M, Niemegeers CJE (1983) Role and localization of serotonin-2 (S2)-receptor-binding sites: Effects of neuronal lesions. In: Mandel P, DeFeudis FV (eds) CNS receptors: From molecular pharmacology to behaviour. Raven Press, New York, pp 373–383

  122. List SJ, Seeman P (1981) Resolution of dopamine and serotonin receptor components of 3H-spiperone binding to rat brain regions. Proc Natl Acad Sci USA 78:2620–2624

  123. Lucki I, Frazer A (1982) Prevention of the serotonin syndrome in rats by repeated administration of monoamine oxidase inhibitors but not tricyclic antidepressants. Psychopharmacology 77:205–211

  124. Maas JW (1975) Biogenic amines and depression. Biochemical and pharmacological separation of two types of depression. Arch Gen Psychiatr 32,1357–1361

  125. Maggi A, Enna SJ (1980) Regional alterations in rat brain neurotransmitter systems following chronic lithium treatment. J Neurochem 34:888–892

  126. Maggi A, U'Prichard DC, Enna SJ (1980) Differential effects of antidepressant treatment on brain monaminergic receptors. Eur J Pharmacol 61:91–98

  127. Maitre L, Baumann PA, Jaeckel J, Waldmeier PC (1982) 5-HT uptake inhibitors: Psychopharmacological and neurobiological criteria of selectivity. In: Ho BT, Schoolar JC, Usdin E (eds) Serotonin in biological psychiatry, Raven Press, New York, pp 229–246

  128. Maj J, Sowinska H, Baran L, Ganarczyk L, Rawlow A (1978) The central antiserotonergic action of mianserin. Psychopharmacology 59:79–84

  129. Marko EJ, Meek JL (1979) The effects of antidepressants on serotonin turnover in discrete regions of rat brain. Naunyn-Schmiedebergs Arch Pharmacol 306:75–79

  130. Martin LL, Sanders-Bush E (1982) Comparison of the pharmacological characteristics of 5-HT1 and 5-HT2 binding sites with those of serotonin autoreceptors which modulate serotonin release. Naunyn-Schmiedebergs Arch Pharmacol 321:165–170

  131. Meek J, Werdinius B (1970) 5-Hydroxytryptamine turnover decreased by the antidepressant drug chlorimipramine. J Pharm Pharmacol 22:141–143

  132. Meltzer HY, Arora RC, Baber R, Tricou BJ (1981a) Serotonin uptake in blood platelets of psychiatric patients. Arch Gen Psychiatry 38:1322–1326

  133. Meltzer HY, Simonovic M, Sturgeon RD, Fang VS (1981b) Effect of antidepressants, lithium and electroconvulsive shock treatment on rat serum prolactin levels. Acta Psychiatr Scand (Suppl 63) 290:100–121

  134. Meltzer HY, Arora RC, Goodnick P (1983) Effect of lithium carbonate on serotonin uptake in blood platelets of patients with affective disorders. J Affect Dis 5:215–221

  135. Mendlewicz U, Pinder RM, Stulemeijerm SM, Van Dorth R (1982) Monoamine metabolites in cerebrospinal fluid of depressed patients during treatment with mianserin or amitriptyline. J Affect Dis 4:219–226

  136. Menkes DB, Aghajanian GK (1981) Alpha-1-adrenoceptor-mediated responses in the lateral geniculate nucleus are enhanced by chronic antidepressant treatment. Eur J Pharmacol 74:27–35

  137. Menkes DB, Aghajanian GK, McCall RB (1980) Chronic antidepressant treatment enhances alpha-adrenergic and serotonergic responses in the facial nucleus. Life Sci 27:45–55

  138. Minchin MCW, Williams J, Bowdler JM, Green AR (1983) The effect of electroconvulsive shock on the uptake and release of noradrenaline and 5-hydroxytryptamine in rat brain slices. J Neurochem 40:765–768

  139. Mogilnicka E (1981) REM sleep deprivation changes behavioural response to catecholaminergic and serotonergic receptor activation in rats. Pharmacol Biochem Behav 15:149–151

  140. Mogilnicka E, Klimek V (1979) Mianserin, danitracen and amitriptyline withdrawal increases the behavioural responses of rats to L-5-HTP. J Pharm Pharmacol 31:704–705

  141. Mogilnicka E, Arbilla S, Depoortere H, Langer SZ (1980) Rapid-eye-movement sleep deprivation decreases the density of 3H-dihydroalprenolol and 3H-imipramine binding sites in the rat cerebral cortex. Eur J Pharmacol 65:289–292

  142. Murphy DL, Campbell I, Costa E (1978) Current status of the indoleamine hypothesis of affective disorders. In: Lipton MA, DiMaschio A, Killam KF (eds) Psychopharmacology: A generation of progress. Raven Press, New York, pp 1235–1248

  143. Murphy DL, Lipper S, Pickar D, Jimerson D, Cohen RM, Garrick NA, Alterman IS, Campbell IC (1981) Selective inhibition of monoamine oxidase type A. Clinical antidepressant effects and metabolic changes in man. In: Youdim MBH, Paykel ES (eds) Monoamine oxidase inhibitors — the state of the art. Whiley, Chichester, pp 189–205

  144. Myers RD, Evans JE, Yaksh TL (1972) Ethanol preference in the rat: Interactions between brain serotonin and ethanol, acetaldehyde, paraldehyde, 5-HTP and 5-HTOL. Neuropharmacology 11:539–549

  145. Nagayama H, Hintgen JN, Aprison MH (1980) Pre- and postsynaptic serotonergic manipulations in an animal model of depression. Pharmacol Biochem Behav 13:575–579

  146. Nagayama H, Hintgen JN, Aprison MH (1981) Postsynaptic action by four antidepressive drugs in an animal model of depression. Pharmacol Biochem Behav 15:125–130

  147. Nelson DL, Herbet A, Enjalbert A, Bockaert J, Hamon M (1980a) Serotonin-sensitive adenylate cyclase and [3H]serotonin binding sites in the CNS of the rat. I. Kinetic parameters and pharmacological properties. Biochem Pharmacol 29:2445–2453

  148. Nelson DL, Herbet A, Adrien J, Bockaert J, Hamon M (1980b) Serotonin-sensitive adenylate cyclase and [3H]serotonin binding sites in the CNS of the rat. II. Respective regional and subcellular distributions and ontogenetic developments. Biochem Pharmacol 29:2455–2463

  149. Nielsen EB, Nielsen M, Ellison G, Braestrup C (1980) Decreased spiroperidol and LSD binding in rat brain after continuous amphetamine. Eur J Pharmacol 66:149–154

  150. Nimgaonkar VL, Green AR, Cowen PJ, Heal DJ, Grahame-Smith DG, Deakin JFW (1983) Studies on the mechanisms by which clenbuterol, a beta-adrenoceptor agonist, enhances 5-HT-mediated behaviour and increases metabolism of 5-HT in the brain of the rat. Neuropharmacology 22:739–749

  151. Nordin G, Ottosson JO, Roos BE (1971) Influence of convulsive therapy on 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid in endogenous depression. Psychopharmacology 20:315–320

  152. Noreika L, Pastor G, Liebman J (1981) Delayed emergence of antidepressant efficacy following withdrawal in olfactory bulbectomized rats. Pharmacol Biochem Behav 15:393–398

  153. Nutt DJ, Green AR, Grahame-Smith DG (1980) Enhanced 5-hydroxytryptamine and dopamine-mediated behavioural responses following convulsions. I. The effects of single and repeated bicuculline-induced seizures. Neuropharmacology 19:897–900

  154. Ogren S-O, Fuxe K, Agnati LF, Gustafsson JA, Jonsson G, Holm AC (1979) Reevaluation of the indoleamine hypothesis of depression. Evidence for a reduction of functional activity of central 5-HT systems by antidepressant drugs. J Neural Transm 46:85–103

  155. Ogren S-O, Ross SB, Hall H, Holm A-C, Renyi AL (1981) The pharmacology of zimelidine: A 5-HT selective reuptake inhibitor. Acta Psychiatr Scand (Suppl 63) 290:127–151

  156. Ogren S-O, Fuxe K, Archer T, Johansson G, Holm AC (1982) Behavioural and biochemical studies on the effects of acute and chronic administration of antidepressant drugs on central serotonergic receptor mechanisms. In: Langer SZ, Takahashi R, Segawa T, Briley M (eds) New vistas in depression. Pergamon Press, New York, pp 11–19

  157. Olpe HR (1981) Differential effect of chlorimipramine and clorgyline on the sensitivity of cortical neurons to serotonin. Eur J Pharmacol 69:375–377

  158. Olpe HR, Schellenberg A (1981) The sensitivity of cortical neurons to serotonin: Effect of chronic treatment with antidepressants, serotonin-uptake inhibitors and monoamine-oxidase-blocking drugs. J Neural Transm 51:233–244

  159. Ortmann R, Martin S, Radeke E, Delina-Stula E (1981) Interaction of beta-adrenoceptor agonists with the serotonergic system in rat brain. A behavioural study using the 5-HTP syndrome. Naunyn-Schmidebergs Arch Pharmacol 316:225–230

  160. Papeschi R, McClure DJ (1971) Homovanillic and 5-hydroxyindoleacetic acid in cerebrospinal fluid of depressed patients. Arch Gen Psychiatry 25:354–358

  161. Paul SM, Rehavi M, Skolnick P, Ballenger JC, Goodwin FK (1981) Depressed patients have decreased binding of tritiated imipramine to platelet serotonin “transporter”. Arch Gen Psychiatr 38:1315–1317

  162. Pawlowski L, Stach R, Kacz D (1982) Chronic treatment with amitriptyline and zimelidine: Attenuation of serotonin-induced changes in the light-evoked responses from the occipital cortex. In: Langer SZ, Takahashi R, Segawa T, Briley M (eds) New vistas in depression. Pergamon Press, New York, pp 73–80

  163. Pedersen OL, Kragh-Sorensen P, Bjerre M, Overo KF, Gram LF (1982) Citalopram, a selective serotonin reuptake inhibitor: Clinical antidepressive and long-term effect — a phase II study. Psychopharmacology 77:199–204

  164. Peroutka SJ, Snyder SH (1980a) Long-term antidepressant treatment decreases spiroperidol-labelled serotonin receptor binding. Science 210:88–90

  165. Peroutka SJ, Snyder SH (1980b) Regulation of serotonin-2 (5-HT2) receptors labelled with [3H] spiroperidol by chronic treatment with the antidepressant amitriptyline. J Pharmacol Exp Ther 215:582–586

  166. Peroutka SJ, Snyder SH (1981) Two distinct serotonin receptors: Regional variations in receptor binding in mammalian brain. Brain Res 208:339–347

  167. Peroutka SJ, Snyder SH (1982) Recognition of multiple serotonin receptor binding sites. In: Ho BT, Schoolar JC, Usdin E (eds) Serotonin in biological psychiatry. Raven Press, New York, pp 155–172

  168. Peroutka SJ, Lebovitz RM, Snyder SH (1981) Two distinct central serotonin receptors with different physiological functions. Science 212:827–829

  169. Plenge P, Mellerup, ET (1982) 3H-Imipramine high-affinity sites in rat brain. Effects of imipramine and lithium. Psychopharmacology 77:94–97

  170. Post RM, Goodwin FK (1974) Effects of amitriptyline and imipramine on amine metabolites in the cerebrospinal fluid of depressed patients. Arch Gen Psychiatry 30:234–239

  171. Quineaux N, Scuvee-Moreau J, Dresse A (1982) Inhibition of in vitro and ex vivo uptake of noradrenaline and 5-hydroxytryptamine by five antidepressants: Correlation with reduction of spontaneous firing rate of central monaminergic neurons. Naunyn-Schmiedebergs Arch Pharmacol 319:66–70

  172. Racagni G, Moccetti I, Calderini G, Battistella A, Brunello N (1983) Temporal sequence of changes in rat central noradrenergic system of rat after prolonged antidepressant treatment: Receptor desensitization and neurotransmitter interactions. Neuropharmacology 22:415–424

  173. Raisman R, Briley MS, Bouchami F, Sechter D, Zarifian E, Langer SZ (1982) 3H-imipramine binding and serotonin uptake in platelets from untreated patients and control volunteers. Psychopharmacology 77:332–335

  174. Ramsey TA, Mendels J (1981) Lithium ion as an antidepressant. In: Enna SJ, Malick JB, Richelson E (eds) Antidepressants: Neurochemical, behavioural and clinical perspectives. Raven Press, New York, pp 175–182

  175. Randrup A, Braestrup C (1977) Uptake inhibition of biogenic amines by newer antidepressant drugs: Relevance to the dopamine hypothesis of depression. Psychopharmacology 53:309–314

  176. Renyi L (1984) Blockade of the serotonin syndrome induced by 5-methoxy-N,N-dimethyl-tryptamine after repeated treatment of rats with amiflamine and some other monoamine oxidase inhibitors. Abstr 14th CINP, Florence, p 409

  177. Richards GE, Holland FJ, Aubert ML, Ganong WF, Kaplan SL, Grumbach MM (1980) Regulation of prolactin and growth hormone secretion. Neuroendocrinology 30:139–143

  178. Risch SC, Janowsky DS, Huey LY (1981) Plasma levels of tricyclic antidepressants and clinical efficacy. In: Enna SJ, Malick JB, Richelson E (eds) Antidepressants: Neurochemical, behavioural and clinical perspectives. Raven Press, New York, pp 183–207

  179. Robertson MM, Trimble MR (1982) Major tranquillizers used as antidepressants. A review. J Affect Disord 4:173–193

  180. Rockman GE, Amit Z, Carr G, Brown ZW, Ogren S-O (1979a) Attenuation of ethanol intake by 5-hydroxytryptamine uptake blockade in laboratory rats. I. Involvement of brain 5-hydroxytryptamine in the mediation of the positive reinforcing properties of alcohol. Arch Int Pharmacodyn Ther 241:245–259

  181. Rockman GE, Amit Z, Carr G, Ogren S-O (1979b) Attenuation of ethanol intake by 5-hydroxytryptamine uptake blockade in laboratory rats: II. Possible interaction with brain noradrenaline. Arch Int Pharmacodyn Ther 241:260–265

  182. Rockman GE, Amit Z, Bourque C, Brown ZW, Ogren S-O (1980) Reduction of voluntary morphine consumption following treatment with zimelidine. Arch Int Pharmacodyn Ther 244:123–129

  183. Ross SB, Renyi AL (1969) Inhibition of the uptake of tritiated 5-HT in brain tissue. Eur J Pharmacol 4:270–277

  184. Ross SB, Aperia B, Beck-Friis J, Jansa S, Wetterberg L, Aberg A (1980) Inhibition of 5-hydroxytryptamine uptake in human platelets by antidepressant agents in vivo. Psychopharmacology 67:1–7

  185. Ross SB, Hall H, Renyi AL, Westerlund D (1981) Effects of zimelidine on serotonergic and noradrenergic neurons after repeated administration in the rat. Psychopharmacology 72:219–225

  186. Rowland N, Antelman SM, Chiodo LA, DeGiovanni L, Kocan D (1982) Differences among serotonergic anorectics and interactions with stress and antidepressants. In: Ho BT, Schoolar JC, Usdin E (eds) Serotonin in biological psychiatry. Raven Press, New York, pp 318–319

  187. Sakai Y, Deguchi T (1980) Effects of mianserin on functions of ascending and descending monoaminergic systems using experimental models. Folia Pharmacol Japan 76:213–225

  188. Sangdee C, Franz DN (1980) Lithium enhancement of central 5-HT transmission induced by 5-HT precursors. Biol Psychiatry 5:59–75

  189. Santos R, Carlini EA (1983) Serotonin receptor activation in rats previously deprived of REM sleep. Pharmacol Biochem Behav 18:501–507

  190. Savage DD, Mendels J, Frazer A (1980) Monoamine oxidase monoamine oxidase inhibitors and serotonin reuptake inhibitors on 3H-serotonin receptor binding in rat brain. Eur J Pharmacol 58:87–88

  191. Savage DD, Mensels J, Frazer A (1980) Monoamine oxidase inhibitors and serotonin uptake inhibitors: Differential effects on [3H]serotonin binding sites in rat brain. J Pharmacol Exp Ther 212:259–263

  192. Scott M, Reading HW, Loudon JB (1979) Studies on human blood platelets in affective disorder. Psychopharmacology 50:131–135

  193. Scuvee-Moreau JJ, Dresse AE (1979) Effect of various antidepressant drugs on the spontaneous firing rate of locus coeruleus and dorsal raphe neurons in the rat. Eur J Pharmacol 57:219–225

  194. Sechter D, Poirier MF, Loo H (1984) Clinical studies with indalpine: A critical review. Clin Neuropharmacol (Suppl 1) 7:870–871

  195. Segawa T, Mizuta T, Nomura T (1979) Modification of central 5-hydroxytryptamine binding sites in synaptic membranes from rat brain after long-term administration of tricyclic antidepressants. Eur J Pharmacol 58:75–83

  196. Segawa T, Mizuta T, Uehara M (1982) Role of the central serotonergic system as related to the pathogenesis of depression: Effect of antidepressants on rat central serotonergic activity. In: Langer SZ, Takahashi R, Segawa T, Briley M (eds) New vistas in depression. Pergamon Press, New York, pp 3–10

  197. Sherman A (1979) Time course of the effects of antidepressants on serotonin in rat neocortex. Commun Psychopharmacol 3:1–5

  198. Shields PJ (1972) Effects of electroconvulsive shock on the metabolism of 5-hydroxytryptamine in the rat brain. J Pharm Pharmacol 24:919–920

  199. Siwers B, Ringberger VA, Tuck R, Sjoqvist F (1976) Initial clinical trial based on clinical methodology of zimelidine (a serotonin uptake inhibitor) in depressed patients. Clin Pharmacol Ther 21:194–200

  200. Stark P, Hardison CD (1984) A composite view of fluoxetine: A new alternative in the treatment of major depressive disorder. Abstr 14th CINP, Florence, p 1152

  201. Steiner JA, Grahame-Smith DG (1980) The effect of repeated electroconvulsive shock on corticosterone responses to centrally acting pharmacological stimuli in the male rat. Psychopharmacology 71:205–212

  202. Stolz JF, Marsden CA (1982) Withdrawal from chronic treatment with metergoline, dl-propranolol and amitriptyline enhances serotonin receptor mediated behaviour in the rat. Eur J Pharmacol 79:17–22

  203. Stolz JF, Marsden CA, Middlemiss DN (1983) Effect of chronic antidepressant treatment and subsequent withdrawal on [3H]-5-hydroxytryptamine and [3H]-spiperone binding in rat frontal cortex and serotonin receptor mediated behaviour. Psychopharmacology 80:150–155

  204. Sugrue MF (1980) Changes in rat brain monoamine turnover following chronic antidepressant administration. Life Sci 26:423–429

  205. Sugrue MF (1983) Some effects of chronic antidepressant treatments on rat brain monoaminergic systems. J Neural Transm 57:281–295

  206. Svensson TH (1978) Attenuated feedback inhibition of brain serotonin synthesis following chronic administration of imipramine. Naunyn-Schmiedebergs Arch Pharmacol 302: 121–131

  207. Svensson TH (1980) Effect of chronic treatment with tricyclic antidepressant drugs on identified brain noradrenergic and serotonergic neurons. Acta Psychiatr Scand (Suppl) 280:121–131

  208. Syvalahti E, Nagy A, Van Praag HM (1979) Effects of zimelidine, a selective 5-HT uptake inhibitor, on serum prolactin levels in man. Psychopharmacology 64:251–253

  209. Takahashi R, Tateishi T, Yoshida H, Hironaka I (1982) Effects of chronic treatment with antidepressant drugs on serotonergic receptor binding activity in normal and tetrabenazine depression rat. In: Langer SZ, Takahashi R, Segawa T, Briley M (eds) New vistas in depression. Pergamon Press, New York, pp 29–36

  210. Tang SW, Seeman P (1980) Effect of antidepresant drugs on serotonergic and adrenergic receptors. Naunyn-Schmiedebergs Arch Pharmacol 311:255–261

  211. Tang SW, Seeman P, Kwan S (1981) Differential effect of chronic imipramine and amitriptyline treatment on rat brain adrenergic and serotonergic receptors. Psychiatry Res 4:129–138

  212. Taylor DP, Allen LE, Ashworth EM, Becker JA, Hyslop DK, Riblet LA (1981) Treatment with trazodone plus phenoxybenzamine accelerates development of decreased type 2 serotonin binding in rat cortex. Neuropharmacology 20:513–516

  213. Traskman L, Asberg M, Bertilsson L, Cronholm B, Mellstrom B, Neckers LM, Sjoqvist F, Thoren P, Tybring G (1979) Plasma levels of chlorimipramine and its desmethyl metabolite during treatment of depression. Clin Pharmacol Ther 26:600–610

  214. Treiser S, Kellar KJ (1980) Lithium: Effects on serotonin receptors in rat brain. Eur J Pharmacol 64:183–185

  215. Tucker DM, Stenslie CE, Roth RE, Shearer SL (1981) Right frontal lobe activation and right hemisphere performance decrement during a depressed mood. Arch Gen Psychiatry 38:169–174

  216. Tuomisto J, Tukainen E, Ahlfors UG (1979) Decreased uptake of 5-hydroxytryptamine in blood platelets from patients with endogenous depression. Psychopharmacology 65:141–147

  217. Tyrer P (1979) Clinical use of monoamine oxidase inhibitors. In: Paykel ES, and Coppen A (eds) Psychopharmacology of affective disorders. Oxford University Press, Oxford, pp 158–178

  218. Van Praag HM (1982) Serotonin precursors in the treatment of depression. In: Ho BT, Schoolar JC, Usdin E (eds) Serotonin in biological psychiatry. Raven Press, New York, pp 259–286

  219. Van Wijk M, Meisch JJ, Korf J (1977) Metabolism of 5-hydroxytryptamine and levels of tricyclic antidepressant drugs in rat brain after acute and chronic treatment. Psychopharmacology 55:217–223

  220. Vetulani J, Lebrecht U, Nowak JZ (1981) Enhancement of responsiveness of the central serotonergic system and serotonin-2 receptor density in rat frontal cortex by electroconvulsive shock treatment. Eur J Pharmacol 81:85

  221. Vogel GW (1975) A review of REM sleep deprivation. Arch Gen Psychiatry 32:749–761

  222. Waldmeier PC, Felner AE, Maitre L (1981) Long term effects of selective MAO inhibitors on MAO activity and amine metabolism. In: Youdim MBH, Paykel ES (eds) Monoamine oxidase inhibitors: The state of the art. Wiley, London, pp 87–102

  223. Wang RY, Aghajanian GK (1980) Enhanced sensitivity of amygdaloid neurons to serotonin and norepinephrine after chronic antidepressant treatment. Commun Psychopharmacol 4:83–90

  224. Whitaker PM, Warsch JJ, Stancer HC, Persad E, Vint CK (1984) Seasonal variation in platelet 3H-imipramine binding: Comparable values in control and depressed populations. Psychiatry Res 11:127–131

  225. Wielosz M, Kleinrok Z (1979) Lithium-induced head twitches in rats. J Pharm Pharmacol 31:410–411

  226. Willoughby JO, Menadue M, Jervois P (1980) Function of serotonin in physiologic secretion of growth hormone and prolactin: Action of 5,7-dihydroxytryptamine, fenfluramine and p-chlorophenylalanine. Brain Res 249:291–299

  227. Willner P (1983) Dopamine and depression: A review of recent evidence. III. The effects of antidepressant treatments. Brain Res Rev 6:237–246

  228. Willner P (1985) Depression: A psychobiological synthesis. Wiley, New York (in press)

  229. Wirz-Justice A, Krauchi K, Lichtsteiner M, Feer H (1978) Is it possible tomodidy serotonin receptor sensitivity? Life Sci 23:1249–1254

  230. Zis AP, Goodwin FK (1979) Novel antidepressants and the biogenic amine hypothesis of depression. The case for iprindole and mianserin. Arch Gen Psychiatry 36:1097–1107

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Willner, P. Antidepressants and serotonergic neurotransmission: An integrative review. Psychopharmacology 85, 387–404 (1985). https://doi.org/10.1007/BF00429653

Download citation

Key words

  • 5-HT
  • Antidepressant drugs
  • ECS