Abstract
Levels of the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in the CSF of rats at various times after repeated electroshock treatment (EST) or chronic administration of haloperidol. The acidic metabolites were analyzed in 25 μl CSF using HPLC with an electrochemical detector. A significant decrease in the CSF levels of DOPAC and HVA was found 4 days after the last administration of chronic haloperidol, EST, or both. The decrease in the level of the dopamine metabolites indicated a slower dopamine turnover, which might have resulted from hypersensitivity of presynaptic dopamine receptors after these treatments. Rats treated with haloperidol also showed an increase in 5-HIAA levels, possibly due to enhanced serotonin turnover. The 5-HIAA increase following haloperidol was prevented by a concurrent administration of EST, suggesting attenuation by EST of the haloperidol-induced enhancement of serotonin turnover.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Atterwill CK (1980) Lack of effect of repeated electroconvulsive shock on3H-spiroperidol and3H-5-HT binding and cholinergic parameters in rat brain. J Neurochem 35:729–734
Barkai AI (1979) Serotonin turnover in the intact rabbit brain: Relation to extracellular proteins and modification by pentobarbital or haloperidol. J Pharmacol Exp Ther 208:44–48
Barkai AI (1981) Myo-Inositol turnover in the intact rat brain: Increased production afterd-amphetamine. J Neurochem 36:1485–1491
Barkai AI, Kowalik S, Reches A, Fahn S (1983) Electroconvulsive treatment attenuates haloperidol-induced increase of3H-imipramine binding in rat brain. Abstr Soc Neurosci 9:229
Bergstrom DA, Kellar KJ (1979) Effect of electroconvulsive shock on monoamine receptor binding sites in rat brain. Nature, 278:464–466
Burt DR, Creese I, Snyder SH (1979) Antischizophrenic drugs: Chronic treatment elevates dopamine receptor binding in brain. Science 196:326–328
Chiodo LA, Antelman SM (1980) Electroconvulsive shock: Progressive dopamine autoreceptor subsensitivity independent of repeated treatment. Science 210:799–801
Crane GE (1968) Tardive dyskinesia in patients treated with major neuroleptics: A review of the literature. Am J Psychiatry (Suppl) 124:40–48
Cross AJ, Deakin JFW, Lofthouse R, Longden A, Owen F, Poulter M (1979) On the mechanism of action of electroconvulsive therapy: Some behavioral and biochemical consequences of repeated electrically induced seizures in rats. Br J Pharmacol 66:111
Deakin JFW, Owen F, Cross AJ, Dashwood MJ (1981) Studies on possible mechanisms of electroconvulsive therapy: Effects of repeated electrically induced seizures on rat brain receptors for monoamines and other neurotransmitters Psychopharmacology 73:345–349
Evans JPM, Grahame-Smith DG, Green AR, Torodoff AFC (1976) Electroconvulsive shock increases the behavioral responses of rats to brain 5-hydroxytryptamine accumulation and central nervous system stimulant drugs. Br J Pharmacol 56:193–199
Fadda F, Argiolas A, Stefanini E, Gessa GL (1977) Differential effect of psychoactive drugs on dihydroxyphenylacetic acid (DOPAC) in the rat substantia nigra and caudate nucleus. Life Sci 21:411–418
Green AR, Deakin JFW (1980) Brain noradrenaline depletion prevents ECS-induced enhancement of serotonin and dopamine mediated behavior. Nature 285:232–233
Green AR, Heal DJ, Grahame-Smith DG (1977) Further observation on the effect of repeated electroconvulsive shock on the behavioral responses of rats produced by increases in the functional activity of 5-hydroxytryptamine and dopamine. Psychopharmacology 52:195–200
Lerer V, Jabotinsky-Rubin K, Bannet J, Ebstain RP, Belmaker RH (1982) Electroconvulsive shock prevents dopamine receptor supersensitivity. Eur J Pharmacol 80:131–134
Leysen JE, Nimegeers CJE, Tollenaere JP, Laduron PM (1978) Serotonergic component of neuroleptic receptors. Nature 272:168–171
Meller E, Friedhoff AJ, Friedman E (1980) Differential effect of acute and chronic haloperidol treatment on striatal and nigral 3,4-dihydroxyphenylacetic acid (DOPAC) levels. Life Sci 26:541–547
Modigh K (1976) Electroconvulsive shock and postsynaptic catecholamine effects: Increased psychomotor stimulant action of apomorphine and clonidine in reserpine-pretreated mice by repeated ECS. J Neural Transm 36:19–32
Modigh K (1979) Long-lasting effects of ECT on monoaminergic mechanisms. In: Brener B, Saletu P, Hollister L (eds) Neuropsychopharmacology, Pergamon, Oxford, pp 11–20
Nowicky M, Roth R (1977) Presynaptic dopamine receptors: Development of supersensitivity following treatment with flufenazine decanoate. Naunyn Schmiedebergs Arch Pharmacol 300:247–254
Price TRP, Levin R (1978) The effects of electroconvulsive therapy on tardive dyskinesia. Am J Psychiatry 135:991–993
Reches A, Wagner HR, Jiang D, Jackson V, Fahns S (1982) The effect of chronicl-dopa administration on supersensitive pre-and postsynaptic dopaminergic receptors in rat brain. Life Sci 31:37–44
Reches A, Wagner HR, Barkai AI, Jackson V, Yablonskaya-Alter E, Fahn S (1984) Electroconvulsive treatment and haloperidol: Effects on pre- and postsynaptic dopamine receptors in rat brain. Psychopharmacology 83:155–158
Serra G, Argiolas A, Fadda F, Melis MR, Gessa GL (1982) Repeated electroconvulsive shock prevents the sedative effect of small doses of apomorphine. Psychopharmacology 73:194–196
Tepper JM, Nakamura S, Spanis CW, Squire LR, Young SJ, Groves PM (1982) Subsensitivity of catecholaminergic neurons to direct acting agonist after single or repeated electroconvulsive shock. Biol Psychiatry 17:1059–1070
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Barkai, A.I., Kowalik, S. & Reches, A. Dopamine and serotonin metabolites in rat cerebroventricular fluid following withdrawal of haloperidol or electroshock treatment. Psychopharmacology 84, 352–355 (1984). https://doi.org/10.1007/BF00555212
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00555212