Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-22T20:40:32.286Z Has data issue: false hasContentIssue false
  • English
  • Français

Does dopamine play a role in schizophrenia?1

Published online by Cambridge University Press:  09 July 2009

Arvid Carlsson
Arvid Carlsson*
Affiliation:
From the Department of Pharmacology University of Göteborg, Sweden
*
2Address for correspondence: Dr Arvid Carlsson, Department of Pharmacology, University of Goteborg, Sweden.
Get access Rights & Permissions [Opens in a new window]

Synopsis

Inhibition of central dopamine functions appears to be a common basic property of antipsychotic drugs. The mesolimbic and nigrostriatal portions of the dopaminergic system are probably the main targets of these drugs for the mental and the extrapyramidal actions respectively.

Dopaminergic hyperfunction, induced by amphetamines or dopa, may lead to a disturbance mimicking paranoid schizophrenia, lending further support for a key role of dopamine in mental functions.

While a primary disturbance in dopamine function in schizophrenia cannot be ruled out, the intimate relationship between dopaminergic and other neuronal systems must be emphasized. The possible involvement of other amine, aminoacid or peptide transmitters in schizophrenia cannot be disregarded.

Type
Research Article
Information
Psychological Medicine , Volume 7 , Issue 4 , November 1977 , pp. 583 - 597
Copyright
Copyright © Cambridge University Press 1977

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

1

A modified version of the 16th Geoffrey Vickers lecture delivered in February 1977, under the auspices of the Mental Health Research Trust.

References

Aghajanian, G. K. & Bunney, B. S. (1973). Central dopaminergic neurons: neurophysiological identification and responses to drugs. In Frontiers in Catecholamine Research (ed. Snyder, S. H. and Usdin, E.), pp. 643–648. Pergamon Press: New York.CrossRefGoogle Scholar
Aghajanian, G. K. & Bunney, B. S. (1974). Pre- and postsynaptic feedback mechanisms in central dopaminergic neurons. In Frontiers of Neurology and Neuroscience Research (ed. Seeman, P. and Brown, G.M.), pp. 4–11. University of Toronto Press: Toronto.Google Scholar
Aghajanian, G. K. & Bunney, B. S. (1977). Dopamine auto-receptors: pharmacological characterization by micro-iontophoretic single cell recording studies. Naunyn-Schmiedeberg's Archives of Pharmacology 297, 1–8.CrossRefGoogle Scholar
Ahlenius, S. & Engel, J. (1971 a). Effects of small doses of haloperidol on timing behaviour (Letters to the Editor). Journal of Pharmacy and Pharmacology 23, 301–302.CrossRefGoogle Scholar
Ahlenius, S. & Engel, J. (1971 b). Behavioural effects of haloperidol after tyrosine hydroxylase inhibition. European Journal of Pharmacology 15, 187–192.CrossRefGoogle ScholarPubMed
Ahlenius, S. & Engel, J. (1973). On the interaction between pimozide and α-methyl-tyrosine. Journal of Pharmacy and Pharmacology 25, 172–174.CrossRefGoogle Scholar
Ahlenius, S. & Engel, J. (1975). Antagonism by haloperidol of the L-dopa-induced disruption of a successive discrimination in the rat. Journal of Neural Transmission 36, 43–49.CrossRefGoogle ScholarPubMed
Ahlenius, S. & Engel, J. (1977). Potentiation by α-methyltyrosine of the suppression of food-reinforced lever-pressing behaviour induced by antipsychotic drugs. Acta Pharmacologica el Toxicologica 40, 115–125.CrossRefGoogle ScholarPubMed
Ahlenius, S., Carlsson, A. & Engel, J. (1975). Antagonism by baclophen of the d-amphetamine-induced disruption of a successive discrimination in the rat. Journal of Neural Transmission 36, 327–333.CrossRefGoogle ScholarPubMed
Andén, N.-E. (1971). Monoamines and synaptic transmission. In Monoamines, noyaux gris cenlraux el syndrome de Parkinson (ed. de Ajuriaguerra, J. and Gauthier, G.), pp. 61–72. George & Co.: Geneva.Google Scholar
Andén, N.-E. (1972). Dopamines turnover in the corpus striatum and the limbic system after treatment with neuroleptic and anti-acetylcholine drugs. Journal of Pharmacy and Pharmacology 24, 905–906.CrossRefGoogle ScholarPubMed
Andén, N.-E. (1973). Catecholaminereceptor mechanisms in vertebrates. In Frontiers in Catecholamine Research (ed. Snyder, S. H. and Usdin, E.) pp. 661–665. Pergamon Press: New York.CrossRefGoogle Scholar
Andén, N.-E. (1976). The interaction of neuroleptic drugs with striatal and limbic dopaminergic mechanisms. In Antipsychotic Drugs, Pharmacodynamics and Pharmacokinetics (ed. Sedvall, G.), pp. 217–225. Pergamon Press: New York.Google Scholar
Andén, N.-E. & Stock, G. (1973). Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. Journal of Pharmacy and Pharmacology 25, 346–348.CrossRefGoogle ScholarPubMed
Andén, N.-E., Roos, B.-E. & Werdinius, B. (1964). Effects of chlorpromazine, haloperidol and reserpine on the levels of phenolic acids in rabbit corpus striatum. Life Sciences 3, 149–158.CrossRefGoogle Scholar
Andén, N.-E., Butcher, S. G., Corrodi, H., Fuxe, K. & Ungerstedt, U. (1970). Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. European Journal of Pharmacology 11, 303–314.CrossRefGoogle ScholarPubMed
Andén, N.-E., Corrodi, H. & Fuxe, K. (1972). Effect of neuroleptic drugs on central catecholamine turnover assessed using tyrosine- and dopamine-β-hydroxylase inhibitors. Journal of Pharmacy and Pharmacology 24, 177–182.CrossRefGoogle Scholar
Bartholini, G. (1975). Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. Journal of Pharmacy and Pharmacology 28, 429–433.CrossRefGoogle Scholar
Bartholini, G., Haefely, W., Jalfre, M., Keller, H. H. & Pletscher, A. (1972). Effects of clozapine on cerebral catecholaminergic neurone systems. British Journal of Pharmacology 46, 736–740.CrossRefGoogle ScholarPubMed
Bartholini, G., Stadler, H., Gadea-Ciria, M. & Lloyd, K. G. (1975 a). The effect of antipsychotic drugs on the release of neurotransmitters in various brain areas. In Antipsychotic Drugs, Pharmacodynamics and Pharmacokinetics (ed. Sedvall, G.), pp. 105–116. Pergamon Press: New York.Google Scholar
Bartholini, G., Stadler, H. & Lloyd, K. (1975 b). Cholinergic-dopaminergic interregulations within the extrapyramidal system. In Cholinergic Mechanisms (ed. Waser, P. G.), pp. 411–418. Raven Press: New York.Google Scholar
Bartholini, G., Stadler, H., Gadea-Ciria, M. & Lloyd, K. G. (1976). The use of the push-pull cannula to estimate the dynamics of acetylcholine and catecholamines within various brain areas. Neuropharmacology 15, 515–519.CrossRefGoogle ScholarPubMed
Biswas, B. & Carlsson, A. (1977 a). The effect of intracerebro-ventricularly administered GABA on brain monoaminemetabolism. Naunyn-Schmiedeberg's Archives of Pharmacology 299, 41–46.CrossRefGoogle Scholar
Biswas, B. & Carlsson, A. (1977 b). The effect of intraperitoneally administered GABA on brain monoamine metabolism. Naunyn-Schmiedeberg's Archives of Pharmacology 299, 47–51.CrossRefGoogle ScholarPubMed
Biswas, B. & Carlsson, A. (1977 c). Effect of intraperitoneally administered GABA in the locomotor activity of mice (to be published).CrossRefGoogle Scholar
Björklund, A. & Lindvall, O. (1975). Dopamine in dendrites of substantia nigra neurons: suggestions for a role in dentritic terminals. Brain Research 83, 531–537.CrossRefGoogle Scholar
Bowers, M. B. Jr & Rozitis, A. (1974). Regional differences in homovanillic acid concentration after acute and chronic administration of antipsychotic drugs. Journal of Pharmacy and Pharmacology 26, 743–745.CrossRefGoogle ScholarPubMed
Bunney, B. S. & Aghajanian, G. K. (1976). d-Amphetamine-induced inhibition of central dopaminergic neurons: mediation by a striato-nigral feedback pathway. Science 192, 391–393.CrossRefGoogle ScholarPubMed
Bunney, B. S., Walters, J. R., Roth, R. H. & Aghajanian, G. K. (1973). Dopaminergic neurons: effects of anti-psychotic drugs and amphetamine on single cell activity. Journal of Pharmacology and Experimental Therapeutics 185, 560–571.Google Scholar
Bürki, H. R., Ruch, W. & Asper, H. (1975). Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat. Psychopharmacologia (Berlin) 41, 27–33.CrossRefGoogle Scholar
Carlsson, A. (1965). Drugs which block the storage of 5-hydroxytryptamine and related amines. In Handbook of Experimental Pharmacology, New Series, Vol. 19: 5, Hydroxytryptamine and Related Indolealkylamines (ed. Erspamer, V.), pp. 529–592. Springer-Verlag: Berlin.Google Scholar
Carlsson, A. (1975). Antipsychotic drugs and catecholamine synapses. In Catecholamines and Schizophrenia (ed. Matthysse, S. W. and Kety, S.), pp. 57–64. Pergamon Press: Oxford.Google Scholar
Carlsson, A. (1977). The influence of antidepressants on central monoaminergic systems. In Neurotransmission and Disturbed Behaviour (ed. van Praag, H. M.). Erven Bohn B.V.: Amsterdam.Google Scholar
Carlsson, A. & Lindqvist, M. (1963). Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacologica et Toxicologica 20, 140–144.CrossRefGoogle ScholarPubMed
Christiansen, J. & Squires, R. F. (1974). Antagonistic effects of apomorphine and haloperidol on rat striatal synaptosomal tyrosine hydroxylase, Journal of Pharmacy and Pharmacology 26, 367–368.CrossRefGoogle ScholarPubMed
Clement-Cormier, Y. C., Kebabian, J. W., Petzold, G. L. & Greengard, P. (1974). Dopamine-sensitive adenylate cyclase in mammalian brain: a possible site of action of antipsychotic drugs. Proceedings of the National Academy of Sciences of the United States of America 71, 1113–1117.CrossRefGoogle Scholar
Corrodi, H. & Hanson, L. C. F. (1966). Central effects of an inhibitor of tyrosine hydroxylation. Psychopharmacologia (Berlin) 10, 116–125.CrossRefGoogle ScholarPubMed
Cott, J., Carlsson, A., Engel, J. & Lindqvist, M. (1976). Suppression of ethanol-induced locomotor stimulation by GABA-like drugs. Naunyn-Schmiedeberg's Archives of Pharmacology 295, 203–209.CrossRefGoogle ScholarPubMed
Creese, I., Burt, D. R. & Snyder, S. H. (1976). Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192, 481–483.CrossRefGoogle ScholarPubMed
Da Prada, M. & Pletscher, A. (1966). Acceleration of cerebral dopamine turn-over by chlorpromazine. Experientia 22, 465–466.CrossRefGoogle Scholar
Davis, K. L., Hollister, L. E. & Berger, P. A. (1976). Baclofen in schizophrenia. Lancet i, 1245.CrossRefGoogle Scholar
Delay, J. & Deniker, O. (1957). Caractéristiques psychophysiologiques des médicaments neuroleptiques. In Psychotropic Drugs (ed. Garattini, S. and Ghetti, V.), pp. 485–501. Elsevier: Amsterdam.Google Scholar
Engel, J., Liljequist, S. & Johannesen, K. (1975). Behavioural effects of long-term treatment with antipsychotic drugs. In Antipsychotic Drugs, Pharmacodynamics and Pharmacokinetics (ed. Sedvall, G.), pp. 63–71. Pergamon Press: Oxford.Google Scholar
Farnebo, L.-O. & Hamberger, B. (1971). Drug-induced changes in the release of [3H]-monoamines from field stimulated rat brain slices. Acta Physiologica Scandinavica Suppl. 371, 35–44.CrossRefGoogle ScholarPubMed
Felger, H. L. (1965). Depressed hospitalized psychiatric patients treated with chlorprothixene concentrate. Journal of New Drugs 5, 240–248.CrossRefGoogle ScholarPubMed
Forsman, A. (1977). Individual differences in clinical response to an antipsychotic drug. Thesis, pp. 1–33, University of Göteborg.Google Scholar
Forsman, A. & Öhman, R. (1977). Current Therapeutical Research, 21, 245–255.Google Scholar
Forsman, A., Mártensson, E., Nyberg, G. & Öhman, R. (1974). A gas chromatographic method for determining haloperidol. Naunyn-Schmiedeberg's Archives of Pharmacology 286, 113–124.CrossRefGoogle ScholarPubMed
Frederiksen, P. K. (1975). Baclofen in the treatment of schizophrenia. Lancet i, 702–703.CrossRefGoogle Scholar
Freud, S. (1914). On Narcissism – An Introduction (trans. 1962 Strachey, J.), p. 73. Hogarth Press: London.Google Scholar
Freud, S. (1930). Letter to Marie Bonaparte, 15 January 1930. Cited by Jones, E. (1957). In The Life and Work of Sigmund Freud, vol. 3, p. 449. Basic Books: New York.Google Scholar
Gershon, S., Heikimian, L. J., Floyd, A. Jr & Hollister, L. E. (1967). Methyl-p-tyrosine (AMT) in schizophrenia. Psychopharmacologia (Berlin) 11, 189–194.CrossRefGoogle ScholarPubMed
Goldstein, M., Anagnoste, B. & Shirron, C. (1973). The effect of trivastal, haloperidol and dibutyryl cyclic AMP on 14C dopamine synthesis in rat striatum. Journal of Pharmacy and Pharmacology 25, 348–351.CrossRefGoogle ScholarPubMed
Goodwin, F. K., Murphy, D. L., Brodie, H. K. H. & Bunney, W. E. (1971). Levodopa alterations in behaviour. Clinical Pharmacology and Therapeutics 12, 383–396.CrossRefGoogle Scholar
Green, A. R. (1977). Repeated chlorpromazine administration increases a behavioural response of rats to 5-hydroxy-tryptamine receptor stimulation. British Journal of Pharmacology 59, 367–371.CrossRefGoogle ScholarPubMed
Greengard, P. (1975). Presynaptic and postsynaptic roles of cyclic AMP and protein phosphorylation at catecholamin-ergic synapses. In Chemical Tools in Catecholamine Research, vol. 2 (ed. Almgren, O., Carlsson, A. and Engel, J.), pp. 249–256. North-Holland: Amsterdam.Google Scholar
Groves, P. M., Wilson, C. J., Young, S. J. & Rebec, G. V. (1975). Self-inhibition by dopaminergic neurons. Science 190, 522–529.CrossRefGoogle ScholarPubMed
Hökfelt, T., Johansson, O., Fuxe, K., Löfström, A., Goldstein, M., Park, D., Ebstein, R., Fraser, H., Jeffcoate, S., Efendic, S., Luft, R. & Arimura, A. (1975). Mapping and relationship of hypothalamic neurotransmitters and hypothalamic hormones.In Proceedings of the Sixth International Congress of Pharmacology,Helsinki, Finland (ed. Tuomisto, J. and Paasonen, M. K.), 3, 93–110.Google Scholar
Hyttel, J. (1974). Effect of neuroleptics on the disappearance rate of 14C labelled catecholamines formed from 14C tyrosine in mouse brain. Journal of Pharmacy and Pharmacology 26, 588–596.CrossRefGoogle ScholarPubMed
Iversen, L. L., Rogawski, M. A. & Miller, R. J. (1976). Comparison of the effects of neuroleptic drugs on pre- and postsynaptic dopaminergic mechanisms in the rat striatum. Molecular Pharmacology 12, 251–262.Google ScholarPubMed
Jackson, D. M., Andén, N.-E. & Dahlström, A. (1975). A functional effect of dopamine in the nucleus accumbens and in some other dopamine-rich parts of the rat brain. Psychopharmacologia (Berlin) 45, 139–149.CrossRefGoogle ScholarPubMed
Jarvik, M. E. (1965). Drugs used in the treatment of psychiatric disorders. In The Pharmacological Basis of Therapeutics (3rd edn) (ed. Goodman, L. S. and Gilman, A.), pp. 159–214. Macmillan: New York.Google Scholar
Javoy, F., Agid, Y., Bouvet, D. & Glowinski, J. (1974). Changes in neostriatal dopamine metabolism after carbachol or atropine microinjections into the substantia nigra. Brain Research 68, 253–260.CrossRefGoogle ScholarPubMed
Kebabian, J. W. & Greengard, P. (1971). Dopamine-sensitive edenyl cyclase: possible role in synaptic transmission. Science 174, 1346–1349.CrossRefGoogle ScholarPubMed
Kehr, W., Carlsson, A., Lindqvist, M., Magnusson, T. & Atack, C. (1972). Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylase activity. Journal of Pharmacy and Pharmacology 24, 744–747.CrossRefGoogle ScholarPubMed
Kehr, W., Carlsson, A. & Lindqvist, M. (1977). Catecholamine synthesis in rat brain after axotomy: interaction between apomorphine and haloperidol. Naunyn-Schmiedeberg's Archives of Pharmacology 297, 111–117.CrossRefGoogle ScholarPubMed
Klein, D. F. & Davis, J. M. (1969). Diagnosis and Drug Treatment of Psychiatric Disorders. Williams and Wilkins: Baltimore.Google Scholar
Kraepelin, E. (1892). Über die Beeinflussung einfacher psychischer Vorgänge durch einige Arzneimittel p. 227. Gustav Fischer: Jena.Google Scholar
Ladinsky, H., Consolo, S., Bianchi, S., Samanin, R. & Ghezzi, D. (1975). Cholinergic-dopaminergic interaction in the striatum: the effect of 6-hydroxydopamine or pimozide treatment on the increased striatal acetylcholine levels induced by apomorphine, piribedil and d-amphetamine. Brain Research 84, 221–226.CrossRefGoogle ScholarPubMed
Lundborg, P. & Engel, J. (1975). Learning deficits and selective biochemical brain changes in 4-week-old offspring of nursing rat mothers treated with neuroleptics. In Antipsychotic Drugs, Pharmacodynamics and Pharmacokinetics (ed. Sedvall, G.), pp. 261–269. Pergamon Press: Oxford.Google Scholar
Macleod, R. M. & Lehmeyer, J. E. (1974). Studies on the mechanism of the dopamine-mediated inhibition of prolactin secretion. Endocrinology 94, 1077–1085.CrossRefGoogle ScholarPubMed
Magnusson, T., Carlsson, A., Fisher, G. H., Chang, D. & Folkers, K. (1976). Effect of synthetic substance p on monoaminergic mechanisms in brain. Journal of Neural Transmission 38, 89–93.CrossRefGoogle ScholarPubMed
McCann, S. M., Kalra, P. S., Donoso, A. P., Bishop, W., Schneider, H. P. G., Fawcett, C. P. & Krulich, L. (1972). The role of monoamines in the control of gonadotropin and prolactin secretion. In Median Eminence: Structure and Function (ed. Knugge, K. M., Scott, D. F. and Weendl, A.), pp. 224–235. Karger: Basel.Google Scholar
McGeer, P. L., Grewaal, D. S. & McGeer, E. G. (1974). Influence of non-cholinergic drugs on rat striatal acetylcholine levels. Brain Research 80, 211–217.CrossRefGoogle Scholar
Meites, J., Lu, K.-H., Wuttke, W., Welsch, C. W., Nagasawa, H. & Quadri, S. K. (1972). Recent studies on functions and control of prolactin secretion in rats. Recent Progress in Hormone Research 28, 471–526.Google ScholarPubMed
Meltzer, H. Y. & Fang, V. S. (1976). Serum prolactin levels in schizophrenia: effect of antipsychotic drugs. A preliminary report. In Hormones, Behaviour and Psychopathology (ed. Sachar, E. J.). Raven Press: New York.Google Scholar
Meltzer, H. Y. & Stahl, M. (1976). The dopamine hypothesis of schizophrenia: a review. Schizophrenia Bulletin 2, 19–76.CrossRefGoogle ScholarPubMed
Miller, R. J., Horn, A. S. & Iversen, L. L. (1974). The action of neuroleptic drugs on dopamine-stimulated adenosine cyclic 3', 5'monophosphate production in rat neostriatum and limbic forebrain. Molecular Pharmacology 10, 759–766.Google Scholar
Miller, R. J., Horn, A. S. & Iversen, L. L. (1975). Effect of butaclamol on dopamine-sensitive adenylate cyclase in rat striatum. Journal of Pharmacy and Pharmacology 27, 212–213.CrossRefGoogle ScholarPubMed
Möller-Nielsen, I., Fjalland, B., Pedersen, V. & Nymark, M. (1974). Pharmacology of neuroleptics upon repeated administration. Psychopharmacologia (Berlin) 34, 95–104.CrossRefGoogle ScholarPubMed
Nybäck, H. & Sedvall, G. (1970). Further studies on the accumulation and disappearance of catecholamines formed from tyrosine-14C in mouse brain. European Journal of Pharmacology 10, 193–205.CrossRefGoogle ScholarPubMed
Öhman, R., Larsson, M., Nilsson, I. M., Engel, J. & Carlsson, A. (1977). Neurometabolic and behavioural effects of haloperidol in relation to drug levels in serum and brain. Nauyn–Schmiedeberg's Archives of Pharmacology (in the press.)CrossRefGoogle ScholarPubMed
Okada, Y. (1976). Role of GABA in the substantia nigra. In GABA in Nervous System Function (ed. Roberts, E., Chase, T. N. and Tower, D. B.), pp. 235–243. Raven Press: New York.Google Scholar
O'Keefe, R., Sharman, D. F. & Vogt, M. (1970). Effect of drugs used in psychoses on cerebral dopamine metabolism. British Journal of Pharmacology 38, 287–304.CrossRefGoogle Scholar
Otsuka, M., Konishi, S. & Takahaski, T. (1975). Hypothalamic substance p as a candidate for transmitter of primary afferent neurons. Federation Proceedings 34, 1922–1928.Google ScholarPubMed
Pijnenburg, A. J. J., Woodruff, G. N. & van Rossum, J. M. (1973). Ergometrine induced locomotor activity following intracerebral injection into the nucleus accumbens. Brain Research 59, 289–302.CrossRefGoogle ScholarPubMed
Powell, D., Leeman, S. E., Tregear, G. W., Niall, H. D. & Potts, J. T. (1973). Radioimmunoassay for substance P. Nature New Biology 241, 252–254.CrossRefGoogle ScholarPubMed
Roos, B.-E. (1965). Effects of certain tranquillizers on the level of homovanillic acid in the corpus striatum. Journal of Pharmacy and Pharmacology 17, 820–821.CrossRefGoogle ScholarPubMed
Schaar, C. J. & Clemens, J. A. (1974). The role of catecholamines in the release of anterior pituitary prolactin in vitro. Endocrinology 95, 1202–1212.CrossRefGoogle Scholar
Sedvall, G. (ed.) (1975). Antipsychotic Drugs, Pharmacodynamics and Pharmacokinetics. Pergamon Press: Oxford.Google Scholar
Sedvall, G. & Nybäck, H. (1972). Neuroleptikabehandling vid schizofreni. Nordisk Psykiatrisk Tidskrift 26, 323–340.Google Scholar
Sedvall, G. & Nybäck, H. (1973). Effect of clozapine and some other antipsychotic agents on synthesis and turnover of dopamine formed from 14C-tyrosine in mouse brain. Israel Journal of Medical Sciences 9 (Suppl.), 24–30.Google ScholarPubMed
Sedvall, G., Alfredsson, G., Bjerkenstedt, L., Eneroth, P., Fyrö, B., Härnryd, C., Swahn, C.-G., Wiesel, F.-A. & Wode-Helgodt, B. (1975). Selective effects of psychoactive drugs on levels of monoamine metabolites and prolactin in cerebrospinal fluid of psychiatric patients.In Proceedings of the Sixth International Congress of Pharmacology,Helsinki, Finland (ed. Tuomisto, J. and Paasonen, M. K.), 3, 255–267.Google Scholar
Seeman, P. & Lee, T. (1975). Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188, 1217–1219.CrossRefGoogle ScholarPubMed
Seeman, P., Staiman, A., Lee, T. & Chang-Wang, M. (1974). The membrane actions of tranquillizers in relation to neuroleptic-induced Parkinsonism and tardive dyskinesia. In The Phenothiazines and Structurally Related Drugs (ed. Forrest, S., Carr, C. J. and Usdin, E.), pp. 137–148. Raven Press: New York.Google Scholar
Sethy, V. H. & Van Woert, M. H. (1974). Modification of striatal acetylcholine concentration by dopamine receptor agonists and antagonists. Research Communications in Chemical Pathology and Pharmacology 8, 13–28.Google ScholarPubMed
Simpson, G. M., Branchey, M. H. & Shiwastava, R. K. (1976). Baclofen in schizophrenia. Lancet i, 966–967.CrossRefGoogle Scholar
Smith, R. C. & Davis, J. M. (1976). Behavioural evidence for supersensitivity after chronic administration of haloperidol, clozapine, and thioridazine. Life Sciences 19, 725–732.CrossRefGoogle ScholarPubMed
Snyder, S. H., Burt, D. R. & Creese, I. (1976). The dopamine receptor of mammalian brain: direct demonstration of binding to agonist and antagonist states. Society for Neuroscience Symposia 1, 28–49.Google Scholar
Stadler, H., Lloyd, K. G., Gadea-Ciria, M. & Bartholini, G. (1973). Enhanced striatal acetylcholine release by chlor-promazine and its reversal by apomorphine. Brain Research 55, 476–480.CrossRefGoogle Scholar
Stawarz, R. J., Hill, H., Robinson, S. E., Settler, P., Dingell, J. V. & Sulser, F. (1975). On the significance of the increase in homovanillic acid (HVA) caused by antipsychotic drugs in corpus striatum and limbic forebrain. Psychopharmacologia (Berlin) 43, 125–130.CrossRefGoogle ScholarPubMed
Stille, von G. & Lauener, H. (1971). Zur Pharmakologie katatonigener Stoffe. 1. Mitteilung: Korrelation zwischen neuroleptischer Katalepsie und Homovanillinsäuregehalt im C. striatum bei Ratten. Arzneimittel-Forschung 21, 252–255.Google Scholar
Strömbom, U. (1977). Antagonism by haloperidol of locomotor depression induced by small doses of apomorphine. Journal of Neural Transmission 40, 191–194.CrossRefGoogle ScholarPubMed
Trabucchi, M., Cheney, D. L., Racagni, G. & Costa, E. (1975). In vivo inhibition of striatal acetylcholine turnover by L-dopa, apomorphine and (+)-amphetamine. Brain Research 85, 130–134.CrossRefGoogle ScholarPubMed
Ungerstedt, U. (1971). Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiologica Scandinavica Suppl. 367, 1–48.CrossRefGoogle ScholarPubMed
Ungerstedt, U., Ljungberg, T., Hoffer, B. & Siggins, G. (1975). Dopaminergic supersensitivity in the striatum. Advances in Neurology 9, 57–65.Google ScholarPubMed
Wålinder, J. & Carlsson, A. (1973). Potentiation of neuroleptics by catecholamine inhibitors. British Medical Journal i, 551–552.CrossRefGoogle Scholar
Wålinder, J., Skott, A., Carlsson, A. & Roos, B.-E. (1976). Potentiation by metyrosine of thioridazine effects in chronic schizophrenics. Archives of General Psychiatry (Chicago) 33, 501–505.CrossRefGoogle ScholarPubMed
Walters, J. R. & Roth, R. H. (1976). Dopaminergic neurons: an in vivo system for measuring drug interactions with presynaptic receptors. Naunyn-Schmiedeberg's Archives of Pharmacology 296, 5–14.CrossRefGoogle Scholar
Wiesel, F. A. & Sedvall, G. (1975). Effect of antipsychotic drugs on homovanillic acid levels in striatum and olfactory tubercle of the rat. European Journal of Pharmacology 30, 364–367.CrossRefGoogle ScholarPubMed
Zivkovic, B., Guidotti, A., Revuelta, A. & Costa, E. (1975). Effect of thioridazine, clozapine and other antipsychotics on the kinetic state of tyrosine hydroxylase and on the turnover rate of dopamine in striatum and nucleus accumbens. Journal of Pharmacology and Experimental Therapeutics 194, 37–46.Google ScholarPubMed