Agonist-Stimulation of Cerebral Phosphoinositide Turnover Following Long-Term Treatment with Antidepresants

  • Pamela D. Butler
  • Amiram I. Barkai
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 221)


Receptor-mediated stimulation of the formation of inositol phosphates (IP) in cerebral tissue may serve as a useful tool for studying long-term changes in the function of serotonin-2 (5-HT2), alpha-1-adrenergic (al), and muscarinic-cholinergic (musc) receptors. In this study we have evaluated the effects of chronic treatment with various antidepressants on receptor-mediated formation of IP in rat brain. Imipramine (IMI: 10 mg/ kg/day; 14 days), Bupropion (BUPR: 40 mg/kg/day; 14 days), Lithium (Li: 0.5% in diet; 7 days) and electroshock treatment (EST: 20–30 mA/day; 7 days) were investigated. Cross-chopped slices of cerebral cortex from control and treated rats were prelabelled with myo-3H-inositol in HEPES buffer containing 11.1 mM LiC1. Accumulation of IP was measured in the presence and absence of serotonin (5-HT, 10 uM), norepinepherine (NE, 5 uM), and carbamylcholine (CCH, 100 uM). Values for agonist-stimulated IP formation in control rats were: 5-HT=123 ± 5%; NE=268 ± 16%; CCh=205 ± 21% of the basal level. The IP response to 5-HT was significantly lower following BUPR and higher following EST. Responses to NE and CCH were significantly lower following BUPR treatment but were not affected by the other antidepressant treatments. These observations are consistent with results of receptor-binding studies indicating up-regulation of 5-HT2 receptors by EST but are not consistent with studies showing down-regulation of 5-HT2 receptors by IMI and a lack of effect on 5-HT2 receptors by BUPR. Our results are not supportive of the notion, based mainly on [3H]prazosin binding studies, that al receptors are up-regulated by EST as well as by different antidepressant drugs.


Antidepressant Drug Antidepressant Treatment Inositol Phosphate Electroconvulsive Shock Inositol Phospholipid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abdel-Latif, A. A., Metabolism of phosphoinositides. In: Handbook of Neurochemistry, Second Edition (Lajtha, A., ed), Plenum Press, N. Y., 91–131 (1982).Google Scholar
  2. Agranoff, B. W., Murthy, P. and Seguin, E. B., Thrombin-induced phosphodiesteratic cleavage of phosphatidylinositol bisophosphate in human platelets, J. Biol. Chem., 258: 2076–2078 (1983).Google Scholar
  3. Ahluwalia, P. and Singhal, R. L., Monoamine uptake into synaptosomes from various regions of rat brain following lithium administration and withdrawal, Neuropharmacology, 20: 483–487 (1981).CrossRefGoogle Scholar
  4. Allison, J. H., Blisner, M. E., Holland, W. H., Hipps, P. P. and Sherman, W. R., Increased brain myo-inositol-1-phosphate in lithium treated rats, Biochem. Biophys. Res. Commun., 71: 664–670 (1976).CrossRefGoogle Scholar
  5. Banerjee, S. P., Kung, L. S., Riggi, S. J. and Chanda, S. K., Development of B-adrenergic receptor subsensitivity by antidepressants, Nature, 268: 455–456 (1977).CrossRefGoogle Scholar
  6. Bell, R. L., Kennerly, D. A., Stanford, N. and Majerus, P. W., Diglyceride lipase: A pathway for arachidonate release from human platelets, Proc. Natl. Acad. Sci. USA, 76: 3238–3241 (1971).CrossRefGoogle Scholar
  7. Bergstrom, D. A. and Kellar, K. J., Effect of electroconvulsive shock on monoaminergic receptor binding sites in rat brain, Nature, 278: 464–466 (1979).CrossRefGoogle Scholar
  8. Berridge, M. J., Rapid accumulation of inositol triphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol, Biochem. J., 212: 849–858 (1983).Google Scholar
  9. Berridge, M. J., Inositol triphosphate and diacylglycerol as second messengers, Biochem. J., 220: 345–360 (1984).Google Scholar
  10. Berridge, M. J., Downes, C. P. and Hanley, M. R., Lithium amplifies agonistdependent phosphatidylinositol responses in brain and salivary glands, Biochem. J., 206: 587–595 (1982).Google Scholar
  11. Berridge, M. J. and Irvine, R. F., Inositol triphosphate, a novel second messenger in cellular signal transduction, Nature (London), 312: 315–321 (1984).CrossRefGoogle Scholar
  12. Brindley, D. N. and Bowley, M., Drugs affecting the synthesis of glycerides and phospholipids in rat liver, Biochem. J., 148: 461–469 (1975).Google Scholar
  13. Broderick, P. and Lynch, V., Behavioral and biochemical changes induced by lithium and L-tryptophan in muricidal rats, Neuropharmacology, 21: 671–679 (1982).CrossRefGoogle Scholar
  14. Brown, E., Kendall, D. A. and Nahorski, S. R., Inositol phospholipid hydrolysis in rat cerebral cortical slices: I. receptor characterization, J. Neurochem., 42: 1379–1387 (1984).CrossRefGoogle Scholar
  15. Bunney Jr., W. E. and Davis, J. M., Norepinepherine in depressive reactions: a review, Arch. Gen. Psychiatry, 13: 483–494 (1965).CrossRefGoogle Scholar
  16. Charney, D. S., Menkes, D. B., Phil, M. and Heninger, G. R., Receptor sensitivity and the mechanism of action of antidepressant treatment, Arch. Gen. Psychiatry., 38: 1160–1180 (1981).CrossRefGoogle Scholar
  17. Conn, P. J. and Sanders-Bush, E., Selective 5-HT2 antagonists inhibit serotonin stimulated phosphatidylinositol metabolism in cerebral cortex, Neuropharmacology, 23: 993–996 (1984).CrossRefGoogle Scholar
  18. Conn, P. J. and Sanders-Bush, E., Serotonin-stimulated phosphoinositide turnover: mediation by the S2 binding site in rat cerebral cortex but not in subcortical regions, J. Pharm. Exp. Ther., 234: 195–203 (1985).Google Scholar
  19. Cooper, T. B., Suckow, R. F. and Glassman, A., Determination of bupropion and its major basic metabolites in plasma by liquid chromatography with dual wavelength in UV detection, J. Pharm. Sci., 73: 1104–1107 (1984).CrossRefGoogle Scholar
  20. Danielsson, E., Peterson, L.-L., Grundin, R., Ogren, S.-O. and Bartfai, T., Anticholinergic potency of psychoactive drugs in human and rat cerebral cortex and striatum, Life Sci., 36: 1451–1457 (1985).CrossRefGoogle Scholar
  21. Dashieff, R. M., Savage, D. D. and McNamara, J. O., Seizures down-regulate muscarinic cholinergic receptors in hippocampal formation, Brain Res., 235: 327–334 (1982).CrossRefGoogle Scholar
  22. Deakin, J. F. W., Owen, F., Cross, A. J. and Dashwood, M. J., Studies on possible mechanisms of action of electroconvulsive therapy: Effects of repeated electrically induced seizures on rat brain receptors for monoamines and other neurotransmitters, Psychopharmacology, 73: 345–349 (1981).CrossRefGoogle Scholar
  23. Dooley, D. J., Hauser, K. L. and Bittinger, H., Differential decrease of the central beta-adrenergic receptor in the rat after subchronic infusion of desipramine and clenbuterol, Neurochem. Int., 5: 333–338 (1983).CrossRefGoogle Scholar
  24. Fauster, R., Honegger, U. and Weismann, U., Inhibition of phospholipid degradation and changes of the phospholipid pattern by desipramine in cultured human fibroblasts, Biochem. Pharm., 32: 1737–1744 (1983).CrossRefGoogle Scholar
  25. Ferris, R. M. and Beaman, O. J., Burpropion: a new antidepressant drug, the mechanism of action of which is not associated with down-regulation of post-synaptic B-adrenergic, serotonergic (5HT2, alpha2 adrenergic, imipramine and dopaminergic receptors in brain, Neuropharmacology, 22: 1257–1267 (1983).CrossRefGoogle Scholar
  26. Ferris, R. M., White, H. L., Cooper, B. R., Maxwell, R. A., Tang, F. L. M., Beaman, O. J. and Russell, A., Some neurochemical properties of a new antidepressant bupropion hydrochloride (Wellbrutin), Drug Devel. Res., 1: 21–35 (1981).CrossRefGoogle Scholar
  27. Fisher, S. K., Figueiredo, J. C. and Bartus, R. T., Differential stimulation of inositol phospholipid turnover in brain by analogs of oxotremorine, J. Neurochem., 43: 1171–1179 (1984a).CrossRefGoogle Scholar
  28. Fisher, S. K., Van Rooijen, L. A. A. and Agranoff, B. W., Renewed interest in the polyphosphoinositides, Trends Bio. Sci., 53–56 (1984b).Google Scholar
  29. Furukawa, T., Yamada, K., Kohno, Y. and Nagasaki, N., Brain serotonin metabolism with relation to the head twitches elicited by lithium in combination with reserpine in mice, Pharmacol. Biochem. Behav., 10: 547–549 (1979).CrossRefGoogle Scholar
  30. Fuxe, K., Ogren, S.-O., Agnati, L. F., Andersson, K. and Eneroth, P., Effects of subchronic antidepressant drug treatment on central serotonergic mechanisms in the male rat. In: Typical and Atypical Antidepressants: Molecular Mechanisms (Costa, E. and Racagni, G., eds). Raven Press, New York, 91–107 (1982).Google Scholar
  31. Fuxe, K., Ogren, S.-O., Agnati, L. F., Benfenati, F., Fredholm, B., Andersson, K., Zini, I. and Eneroth, P., Chronic antidepressant treatment and central 5-HT synapses, Neuropharm, 22: 389–400 (1983).CrossRefGoogle Scholar
  32. Gandolfi, O., Barbaccia, M. L., Chuang, D. M. and Costa, E., Daily bupropion injections for three weeks attenuate the NE-stimulation of adenylate cyclase and the number of B-adrenergic recognition sites in rat frontal cortex, Neuropharmacology, 22: 927–929 (1983).CrossRefGoogle Scholar
  33. Gonzales, R. A. and Crews, F. T., Characterization of the cholinergic stimulation of phosphoinositide hydrolysis in rat brain slices, J. Neurosci., 4: 3120–3127 (1984).Google Scholar
  34. Gonzales, R. A. and Crews, F. T., Cholinergic-and adrenergic-stimulated inositide hydrolysis in brain: interaction, regional distribution, and coupling mechanisms, J. of Neurochem., 45: 1076–1084 (1985).CrossRefGoogle Scholar
  35. Green, A. R., Heal, D. J., Johnson, P., Laurence, B. E. and Nimgaonkar, V. L., 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 (1983a).CrossRefGoogle Scholar
  36. Green, A. R., Johnson, P. and Nimgaonkar, V. L., Increased 5-HT2 receptor number in brain as a probable explanation for the enhanced 5-hydroxytryptamine-mediated behavior following repeated electroconvulsive shock administration to rats, Br. J. Pharmacol., 80: 173–177 (1983b).CrossRefGoogle Scholar
  37. Halaris, A. E., Stern, W. and Truox-Horto, M. S., Clinical efficacy of the antidepressant bupropion (Wellbutrin), Psychopharm. Bull., 17: 140 (1981).Google Scholar
  38. Hallcher, L. M. and Sherman, W. R., The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphate from bovine brain, J. Bio. Chem., 255: 10896–10901 (1980).Google Scholar
  39. Hauser, G. and Pappu, A. S., Effects of propranolol and other cationic amphiphilic drugs on phospholipid metabolism. In: phospholipids in the Nervous System (Horrocks, L. A., Amsel, G. B. and Porcellati, G. eds) Raven Press, New York, 283–300 (1982).Google Scholar
  40. Hawthorne, J. N. and Pickard, M. R., Phospholipids in synaptic function, J. Neurochem., 32: 4–14 (1979).CrossRefGoogle Scholar
  41. Iversen, L. L. and Mackay, A. V. P., Pharmacodynamics of anti-depressants and antimanic drugs. In: Psychopharmacology of Affective Disorders (Paykel, E. S. and Coppen, A. eds). New York, Oxford University Press Inc., 60–90 (1979).Google Scholar
  42. Janowsky, A., Labarca, R. and Paul, S., Characterization of neurotransmitter receptor-mediated phosphatidylinositol hydrolysis in the rat hippocampus, Life Sciences, 35: 1953–1961 (1984).CrossRefGoogle Scholar
  43. Janowsky, A., Labarca, R. and Paul, S. M., Neurotransmitter receptor-mediated myo-inositol-1-phosphate accumulation in hippocampal slices. In: Inositol and Phosphoinositides: Metabolism and Regulation (Bleasdale, J. E., Eichberg, J., and Hauser, G. eds). Humana Press, Clifton, N.J., 83–90 (1985).CrossRefGoogle Scholar
  44. Jope, R. S., Effects of lithium treatment in vitro and in vivo on acetylcholine metabolism in rat brain, J. Neurochem., 33: 487–495 (1979).CrossRefGoogle Scholar
  45. Kafka, M., Wirz-Justice, A., Naber, D., Marangos, P., O’Donohue, T. and Wehr, T., Effect of lithium on circadian neurotransmitter receptor rhythms, Neuropsychobio., 8: 41–50 (1982).CrossRefGoogle Scholar
  46. Kellar, K. J., Cascio, C. S., Bergstrom, D. A., Butler, J. A. and Iadorola, P., Electroconvulsive shock and reserpine: Effects on B-adrenergic receptors in rat brain, J. Neurochem., 37: 830–836 (1981a).CrossRefGoogle Scholar
  47. Kellar, K. J., Cascio, C. S., Butler, J. A. and Kurtzke, R. N., Differential effects of electroconvulsive shock and antidepressant drugs on serotonin-2 receptors in rat brain, Eur. J. Pharmacol., 69: 515–518 (1981b).CrossRefGoogle Scholar
  48. Kellar, K. J. and Stockmeier, C. A., Effects of ECS and serotonin axon lesions on B-adrenergic and serotonin-2 receptors in rat brain. In: ECT: Clinical and Basic Research Issues (Malitz, S. and Sackeim, H. eds) Ann. N.Y. Acad. Sciences, vol. 452 (1986).Google Scholar
  49. Kendall, D. A., Duman, R., Slopis, J. and Enna, S. J., Influence of adrenocorticotropin hormone and yohimbine on antidepressant-induced declines in rat brain neurotransmitter receptor binding and function, J. Pharmacol. Exp. Ther., 22: 566–571 (1982).Google Scholar
  50. Kendall, D. A. and Nahorski, S. R., 5-Hydroxytryptamine-stimulated inositol phospholipid hydrolysis in rat cerebral cortex slices: pharmacological characterization and effects of antidepressants, J. Pharm. Exp. Ther., 233: 473–479 (1985).Google Scholar
  51. Lerer, B. and Stanley, M., Effect of chronic lithium on cholinergically mediated responses and [3H]QNB binding in rat brain, Br. Res., 344: 211–219 (1985).CrossRefGoogle Scholar
  52. Lerer, B., Stanley, M., Demetriou, S. and Gershon, S., Effect of electroconvulsive shock on muscarinic cholinergic receptors in rat cerebral cortex and hippocampus, J. Neurochem., 6: 1680–1683 (1983).CrossRefGoogle Scholar
  53. Levy, A., Zohar, J. and Belmaker, R. H., The effect of chronic lithium pretreatment on rat brain muscarinic receptor regulation, Neuropharm., 21: 1199–1201 (1982).CrossRefGoogle Scholar
  54. Lullman, H., Luliman-Rauch, R. and Wassermann, O., Drug-induced phospholipidosis, Germ. Med. 3: 128–135 (1973).Google Scholar
  55. Lullman-Rauch, R., Lipodosislike renal changes in rats treated with chlorphentermine or with tricyclic antidepressants, Virchows Arch. B. Cell Pathol., 18: 51–60 (1975).Google Scholar
  56. Maggi, A. and Enna, S. J., Regional alterations in rat brain neurotransmitter systems following chronic lithium treatment, J. Neurochem., 34: 888–892 (1980).CrossRefGoogle Scholar
  57. Malitz, S. and Sackheim, H. eds., ECT: Clinical and Basic Research Issues, Ann. N.Y. Acad. Sciences, Vol. 452 (1986).Google Scholar
  58. Martin, T. F. J., Thyrotropin-releasing hormone rapidly activates the phosphodiesteratic hydrolysis of polyphosphoinositides in GH3 pituitary cells, J. Biol. Chem., 258: 14816–14822 (1983).Google Scholar
  59. Matsuzawa, Y. and Hostetler, K. Y., Inhibition of lysosomal phospholipase A and phospholipase C by chloroquine and 4,4′-Bis(diethylaminoethoxy)a, Bdiethyldiphenylethance, J. Bio. Chem., 255: 5190–5194 (1980).Google Scholar
  60. Maxwell, R. A., Mehta, N. B., Tucker, W. E., Schroeder, D. H. and Stern, W. C., Bupropion. In: Pharmacological and Biochemical Properties of Drug Substances. Vol. 3, (M. E. Goldberg ed.) American Pharmaceutical Association Academy of Pharmaceutical Sciences, Washington, D. C. 1–55 (1981).Google Scholar
  61. Meltzer, H. Y., Serotonergic function in the affective disorders: The effects of antidepressants and lithium on the 5-hydroxytryptophaninduced increase in serum Cortisol. In: Presynaptic Modulation of Postsynaptic Receptors in Mental Diseases, (Salama, A. I. ed.), Annals of the N. Y. Academy of Sciences, vol. 430, 115–137 (1984).Google Scholar
  62. Micheli, R. H., Inositol phospholipids and cell surface receptor function, Biochim. Biophys. Acta, 415: 81–147 (1975).CrossRefGoogle Scholar
  63. Nishizuka, Y., Turnover of inositol phospholipids and signal transduction, Science, 225: 1365–1370 (1984a).CrossRefGoogle Scholar
  64. Nishizuka, Y., The role of protein kinase C in cell surface signal transduction and tumor promotion, Nature, 308: 693–698 (1984b).CrossRefGoogle Scholar
  65. Okazaki, T., Sagawa, N., Okita, J. R., Bleasdale, J. E., MacDonald, P. C. and Johnston, J. M., Diacylglycerol metabolism and arachidonic acid release in human fetal membranes and decidual vera, J. Biol. Chem., 256: 7316–7321 (1981).Google Scholar
  66. Oswald, I., Brezinova, V. and Dunleavy, D. L. F., On the slowness of action of tricyclic antidepressant drugs, Br. J. Psychiatry, 120: 673–677 (1972).CrossRefGoogle Scholar
  67. Pandey, G. N., Heinze, W. B., Brown, B. D. and Davis, J. M., Effects of antidepressants on B-adrenergic receptor sensitivity in rat brain, Fedn. Proc. Fedn. Am. Socs. Exp. Biol., 38: 592 (1979a).Google Scholar
  68. Pandey, G. N., Heinze, W. B., Brown, B. D. and Davis, J. M., Electroconvulsive shock treatment decreases B-adrenergic receptor sensitivity in rat brain, Nature, 280: 234–235 (1979b).CrossRefGoogle Scholar
  69. Peroutka, S. J. and Snyder, S. H., Long-term antidepressant treatment decreases spiroperidol-labelled serotonin receptor binding, Science, 210: 88–90 (1980).CrossRefGoogle Scholar
  70. Perumal, A. S., Smith, T. M., Suckow, R. F. and Cooper, T. B., Bupropion and BW306U on B-receptors in mouse and guinea-pig brain, Trans. Am. Soc. Neurochem., 17: 268 (1986).Google Scholar
  71. Rosenblatt, J. E., Pert, C. B., Tallman, J. F., Pert, A. and Bunney Jr., W. E., The effects of imipramine and lithium on a-and B-receptor binding in rat brain, Br. Res., 160: 186–191 (1979).CrossRefGoogle Scholar
  72. Sangdee, C. and Franz, D. N., Lithium enhancement of central 5-HT transmission induced by 5-HT precursors, Biol. Psychiatry, 15: 59–75 (1980).Google Scholar
  73. Schoepp, D. D., Knepper, S. M. and Rutledge, C. O., Norepinepherine stimulation of phosphoinositide hydrolysis in rat cerebral cortex is associated with the alpha1-adrenoceptor, J. Neurochem., 43: 1758–1761 (1984).CrossRefGoogle Scholar
  74. Schildkraut, J. J., The catecholamine hypothesis of depression: A review of supporting evidence, Am. J. Psychiat., 122: 509–522 (1965).Google Scholar
  75. Schildkraut, J. J. and Kety, S. S., Biogenic amines and emotion, Science, 156: 21–30 (1967).CrossRefGoogle Scholar
  76. Sellinger-Barnett, M. M., Mendels, J. and Frazer, A., The effect of psychoactive drugs on B-adrenergic receptor binding sites in rat brain, Neuropharmacology, 19: 447–454 (1980).CrossRefGoogle Scholar
  77. Sherman, W. R., Leavitt, A. L., Honchar, M. P., Hallcher, L. M. and Phillips, B. E., Evidence that lithium alters phosphoinositide metabolism: Chronic administration elevates primarily D-myo-inosital-1-phosphate in cerebral cortex of the rat, J. Neurochem., 36: 1947–1951 (1981).CrossRefGoogle Scholar
  78. Snyder, S. H. and Yamamura, H. I., Antidepressants and the muscarinic acetylcholine receptor, Arch. Gen. Psychiatry., 34: 236–239 (1977).CrossRefGoogle Scholar
  79. Soroko, F. E., Mehta, N. B., Maxwell, R. A., Ferris, R. M. and Schroeder, D. H., Buproprion hydrochloride ((+) a-t-butylamino-3-chloropropiophenone HC1): a novel antidepressant agent, J. Pharm. Pharmac., 29: 767–770 (1977).CrossRefGoogle Scholar
  80. Streb, H., Irvine, R. F., Berridge, M. J. and Schulz, I., Release of Ca from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-l,4,5-triphosphate, Nature (London), 306: 67–69 (1983).CrossRefGoogle Scholar
  81. Suckow, R. F. and Cooper, T. B., Simultaneous determination of imipramine and desipramine and their 2-hydroxy metabolites in plasma by ion-pair reversed-phase high performance liquid chromatography with amperometric detection, J. Pharm. Sci., 70: 257–261 (1981).CrossRefGoogle Scholar
  82. Sulser, F., New perspectives on the mode of action of antidepressant drugs, Trends Pharmacol. Sci., 1: 92–94 (1979).CrossRefGoogle Scholar
  83. Sulser, F., Janowsky, A. J., Okada, F., Manier, D. H. and Mobley, P. L., Regulation of recognition and action function of the norepinepherine (NE) receptor-coupled adenylate cyclase system in brain: implications for the therapy of depression, Neuropharmacology, 22: 425–431 (1983).CrossRefGoogle Scholar
  84. Sulser, F., Vetulani, J. and Mobley, P. L., Mode of action of antidepressant drugs, Biochem. Pharmacol., 27: 257–261 (1978).CrossRefGoogle Scholar
  85. Tang, S. W., Seeman, P. and Kwang, S., Differential effects of chronic desipramine and amitriptyline treatment on rat brain adrenergic and serotonergic receptors, Psychiatry Res., 4: 129–138 (1981).CrossRefGoogle Scholar
  86. Treiser, S. and Kellar, K. J., Lithium effects on serotonin receptors in rat brain, Eur. J. Pharmacol., 64: 83–185 (1980).CrossRefGoogle Scholar
  87. Vetulani, J., Changes in responsiveness of central aminergic structures after chronic ECS. In: ECT: Basic Mechanisms (Lerer, B., Weiner, R. D., and Belmaker, R. H., eds.), Libbey, London, 33–45 (1983).Google Scholar
  88. Vetulani, J. and Antkiewicz-Michaluk, L., Alpha-adrenergic receptor changes during antidepressant treatment, Acta Pharmacologica et Toxicologica, 56, Suppl 1: 55–65 (1985).Google Scholar
  89. Vetulani, J., Lebrecht, U. and Pile, A., Enhancement of responsiveness of the central serotonergic system and serotonin-2 receptor density in rat frontal cortex by electroconvulsive shock treatment, Eur. J. Pharmacol., 76: 81–85 (1981).CrossRefGoogle Scholar
  90. Williams, M., Risley, E. A. and Robinson, J. L., Chronic in vivo treatment with desmethylimipramine and mianserin does not alter adenosine A-1 radioligand binding in rat cortex, Neurosci. Lett., 35: 47–51 (1983).CrossRefGoogle Scholar
  91. Wolfe, B. B., Harden, T. K., Sporn, J. R. and Molinoff, P. B., Presynaptic modulation of Beta adrenergic receptors in rat cerebral cortex after treatment with antidepressants, J. Pharmacol. Exp. Ther., 207: 446–457 (1977).Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Pamela D. Butler
    • 1
  • Amiram I. Barkai
    • 1
  1. 1.New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA

Personalised recommendations