Abstract
l-Tryptophan was administered to rats pretreated with selective inhibitors of the A and B forms of MAO. deprenyl, a selective inhibitor of MAO-B, produced only minor changes in behaviour and in the concentrations of apparent 5-HT and 5-HIAA in brain. High doses of clorgyline, a selective inhibitor of MAO-A, produced a characteristic stereotyped syndrome of hypermotility and tremor as well as an increase in apparent 5-HT and a decrease in apparent 5-HIAA in brain. Small doses of deprenyl and clorgyline in combination, but not singly, produced maximal effects on behaviour as well as on the concentrations of apparent 5-HT and 5-HIAA in brain. Maximum behavioural and biochemical effects were also produced when either deprenyl or clorgyline was administered 18 hrs before the other.
It is concluded that the syndrome may be dependent on the formation of an N-substituted derivative of 5-HT which is at least partly deaminated by MAO-B. Alternatively, the syndrome may be dependent on a sufficiently high concentration of 5-HT in a special compartment where it is partly deaminated by MAO-B.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ahlborg, U., Holmstedt, B., Lindgren, J.-E.: Fate and metabolism of some hallucinogenic indolealkylamines. Advanc. Biol. 6, 213–229 (1968)
Atack, C., Lindqvist, M.: Conjoint native and orthophthaldialdehyde-condensate assays for the fluorimetric determination of 5-hydroxyindoles in brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 267–284 (1973)
Banerjee, S. P., Snyder, S. H.: Methyltetrahydrofolic acid mediates N- and O-methylation of biogenic amines. Science 182, 74–75 (1973)
Carlsson, A., Jonason, J., Lindqvist, M., Fuxe, K.: Demonstration of extraneuronal 5-hydroxytryptamine accumulation in brain following membrane-pump blockade by chlorimipramine. Brain Res. 12, 456–460 (1969)
Corrodi, H.: Blockade of the psychotic syndrome caused by nialamide in mice. J. Pharm. Pharmacol. 18, 197–199 (1966)
Glassman, A. H., Platman, S. R.: Potentiation of a monoamine oxidase inhibitor by tryptophan. J. psychiat. Res. 7, 83–88 (1969)
Goridis, C., Neff, N. H.: Monoamine oxidase in sympathetic nerves: a transmitter specific enzyme type. Brit. J. Pharmacol. 43, 814–818 (1971)
Goridis, C., Neff, N. H.: Evidence for a specific monoamine oxidase associated with sympathetic nerves. Neuropharmacology 10, 557–564 (1971)
Goridis, C., Meek, J. L., Neff, N. H.: Monoamine oxidase of rat spinal cord after transection. Life Sci. 11, Part I, 861–866 (1972)
Grahame-Smith, D. G.: Studies in vivo on the relationship between brain tryptophan, brain 5-HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and L-tryptophan. J. Neurochem. 18, 1053–1066 (1971)
Grahame-Smith, D. G.: Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by L-tryptophan or 5-methoxy-N,N-dirnethyltryptamine in rats treated with a monoamine oxidase inhibitor. Brit. J. Pharmacol. 43, 856–864 (1971)
Hall, D. W. R., Logan, B. W., Parsons, G. H.: Further studies on the inhibition of monoamine oxidase by M & B 9302 (clorgyline)-I. Biochem. Pharmacol. 18, 1447–1454 (1969)
Hess, S. M., Doepfner, W.: Behavioral effects and brain amine content in rats. Arch. int. Pharmacodyn. 134, 89–99 (1961)
Himwich, W. A., Davies, J. M., Forbes, D. J., Glisson, S. N., Magnusson, T., Stout, M. A., Trusty, D. M.: Indole metabolism and behavior in dog. Biol. Psychiat. 4, 51–63 (1972)
Horita, A., Carino, M. A.: Modification of the toxic actions of L-tryptophan by pargyline and p-chlorophenylalanine. Biochem. Pharmacol. 19, 1521–1524 (1970)
Jarrot, B.: Occurrence and properties of monoamine oxidase in adrenergic neurons. J. Neurochem. 18, 7–16 (1971)
Johnston, J. P.: Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem. Pharmacol. 17, 1285–1297 (1968)
Jonsson, J., Lewander, T.: A method for the simultaneous determination of 5-hydroxy-3-indole-acetic acid (5-HIAA) and 5-hydroxy-tryptamine (5-HT) in brain tissue and cerebrospinal fluid. Acta physiol. scand. 78, 43–51 (1970)
Knoll, J., Vizi, E. S., Somogyi, G.: Phenylisopropylmethyl-propynylamine (E-250), a monoaminooxidase inhibitor antagonising the effects of tyramine. Arzneimittel-Forsch. 18, 109–112 (1968)
Koe, B. K., Weissman, A.: p-Chlorophenylalanine: A specific depletor of brain serotonin. J. Pharmacol. exp. Ther. 154, 499–516 (1966)
Korf, J., Valkenburgh-Sikkema, T.: Fluorimetric determination of 5-hydroxyindoleacetic acid in human urine and cerebrospinal fluid. Clin. chim. Acta 26, 301–306 (1969)
Lauer, J. W., Inskip, W. M., Bernsohn, J., Zeller, E. A.: Observations on schizophrenic patients after iproniazid and tryptophan. Arch. Neurol. Psychiat. (Chic.) 80, 122–130 (1968)
McCauley, R., Racker, E.: Separation of two monoamine oxidases from bovine brain. Molec. Cell. Biochem. 1, 73–81 (1973)
Magyar, K., Vizi, E. S., Ecseri, Z., Knoll, J.: Comparative pharmacological analysis of the optical isomers of phenyl-isopropyl-methyl-propinylamine (E-250). Acta physiol. Acad. Sci. hung. 32, 377–387 (1967)
Maickel, R. P., Miller, F. P.: Fluorescent products formed by reaction of indole derivatives and o-phthalaldehyde. Anal. Chem. 38, 1937–1938 (1966)
Modigh, K., Svensson, T. H.: On the role of central nervous system catecholamines and 5-hydroxytryptamine in the nialamide-induced behavioural syndrome. Brit. J. Pharmacol. 46, 32–45 (1972)
Oates, J. A., Sjoerdsma, A.: Neurologic effects of tryptophan in patients receiving a monoamine oxidase inhibitor. Neurology (Minneap.) 10, 1076–1078 (1960)
Sprince, H., Parker, C. M., Jameson, D., Alexander, F.: Urinary indoles in schizophrenic and psychoneurotic patients after administration of tranylcypromine (Parnate) and methionine or tryptophan. J. nerv. ment. Dis. 137, 246–251 (1963)
Squires, R. F.: Additional evidence for the existence of several forms of mitochondrial monoamine oxidase in the mouse. Biochem. Pharmacol. 17, 1401–1409 (1968)
Squires, R. F.: Multiple forms of monoamine oxidase in intact mitochondria as characterized by selective inhibitors and thermal stability: A comparison of eight mammalian species. Advanc. Biochem. Psychopharmacol. 5, 355–370 (1972)
Squires, R. F., Buus Lassen, J.: Some pharmacological and biochemical properties of γ-morpholino-butyrophenone (NSD 2023), a new monoamine oxidase inhibitor. Biochem. Pharmacol. 17, 369–384 (1968)
Svensson, T. H., Thieme, G.: An investigation of a new instrument to measure motor activity of small animals. Psychopharmacologia (Berl.) 14, 157–163 (1969)
Yang, H.-Y. T., Goridis, C., Neff, N. H.: Properties of monoamine oxidases in sympathetic nerve and pineal gland. J. Neurochem. 19, 1241–1250 (1972)
Yang, H.-Y. T., Neff, N. H.: Β-Phenylethylamine: A specific substrate for type B monoamine oxidase of brain. J. Pharmacol. exp. Ther. 187, 365–371 (1973)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Squires, R.F., Buus Lassen, J. The inhibition of A and B forms of MAO in the production of a characteristic behavioural syndrome in rats after l-tryptophan loading. Psychopharmacologia 41, 145–151 (1975). https://doi.org/10.1007/BF00421072
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00421072