Summary
Noradrenaline (NA), dopamine (DA) and DOPAC were determined with a newly developed radioenzymatic method simultaneously in the striatum, limbic system, hypothalamus and in catecholamine-containing cell groups of the rat brain. Only a loose relationship could be established between DOPAC and DA contents in the various brain areas. The lowest relative DOPAC level (DOPAC/DA ratio) was found in the median eminence, while it was the highest in the periventricular nucleus of the hypothalamus. Haloperidol increased the DOPAC level in only part of the nuclei examined (striatum, olfactory tubercle, central amygdaloid nucleus), while in other limbic regions as well as in the hypothalamic dorsomedial, arcuate and paraventricular nuclei it proved to be ineffective. The DOPAC level in the locus coeruleus was decreased by haloperidol. Pargyline caused an appr. 50% decrease of DOPAC content of most of the nuclei in 10 min; the effectivity of the drug did not show parallelism with that of haloperidol. The monoamine oxidase inhibition caused no change in the DOPAC level in the hypothalamic periventricular and paraventricular nuclei. Results are discussed as a consequence of different reactivity of various DA-ergic terminals and catecholamine cell bodies to haloperidol and pargyline.
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References
Andén, N.-E., Roos, B.-E., Werdinius, B. Effects of chlorpromazine, haloperidol and reserpine on the levels of phenolic acids in rabbit corpus striatum. Life Sci.3, 149–158 (1964).
Andén, N.-E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U. Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol.11, 303–314 (1970).
Andén, N.-E., Corrodi, H., Fuxe, K. Effect of neuroleptic drugs on central catecholamine turnover assessed using tyrosine- and dopamine-beta-hydroxylase inhibitors. J. Pharm. Pharmacol.24, 177–182 (1972).
Agid, Y., Javoy, F., Youdim, M. B. H. Monoamine oxidase and aldehyde dehydrogenase activity in the striatum of rats after 6-hydroxydopamine lesion of nigrostriatal pathway. Brit. J. Pharmacol.48, 175–178 (1973).
Argiolas, A., Fadda, F., Stefanini, E., Gessa, G. L. A simple radioenzymatic method for determination of picogram amounts of 3, 4-dihydroxyphenylacetic acid (DOPAC) in the rat brain. J. Neurochem.29, 599 to 601 (1977).
Argiolas, A., Pargletti, E., Fadda, F., Pellegrini Quarantotti, B., Gessa, G. L. Effect of psychotropic drugs on 3, 4-dihydroxyphenylacetic acid (DOPAC) content in the medial basal hypothalamus. Life Sci.22, 461 to 466 (1978).
Bartholini, G. Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. J. Pharm. Pharmacol.28, 429–433 (1976).
Björklund, A., Lindvall, O., Nobin, A. Evidence of incerto-hypothalamic dopamine neurone system in the rat. Brain Res.89, 29–42 (1975).
Brownstein, M., Saavedra, J. M., Palkovlts, M. Norepinephrine and dopamine in the limbic system of the rat. Brain Res.79, 431–436 (1974).
Bunney, B. S., Walters, J. R., Roth, R. H., Aghajanian, G. K. Dopaminergic neurone: effect of antipsychotic drugs and amphetamine on single cell activity. J. Pharmacol. Exp. Ther.185, 560–571 (1973).
Carlsson, A., Lindqvist, M. Effect of chlorpromazine or haloperidol on the formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol. Toxicol.20, 140–144 (1963).
Cheramy, A., Besson, M. J., Glowinski, J. Increased release of dopamine from striatal dopaminergic terminals in the rat after treatment with a neuroleptic: thioproperazine. Europ. J. Pharmacol.10, 206–214 (1970).
Clement-Cornier, Y. C., Kebabian, J. W., Petzold, G. L., Greengard, P. A. Dopamine sensitive adenylate cyclase in mammalian brain: A possible site of action of antipsychotic drugs. Proc. Nat. Acad. Sci. U.S.A.71, 1113–1117 (1974).
Creese, I., Burt, D. R., Snyder, S. H. Dopamine receptor binding: differentation of agonist and antagonist states with3H-dopamine and3H-haloperidol. Life Sci.17, 993–1002 (1975).
Cuello, A. C., Hiley, R., Iversen, L. L. Use of catechol-O-methyltransferase for the enzyme radiochemical assay of dopamine. J. Neurochem.21, 1337–1340 (1973).
Dahlström, A., Fuxe, K. Evidence for the existence of monoaminecontaining neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol. Scand.62, Suppl. 232, 1–65 (1964).
Dunnett, C. W. A multiple comparison procedure for comparing several treatments with a control. J. Amer. Statist. Ass.50, 1096–1121 (1955).
Fadda, F., Argiolas, A., Stefanini, E., Gessa, G. L. Differential effect of psychotropic drugs on dihydroxyphenylacetic acid (DOPAC) in the rat substantia nigra and caudate nucleus. Life Sci.21, 411–418 (1977).
Fekete, M. I. K., Kanyicska, B., Herman, J. P. Simultaneous radioenzymatic assay of catecholamines and dihydroxyphenylacetic acid (DOPAC); comparison of the effects of drugs on the tuberoinfundibular and striatal dopamine metabolism and on plasma prolactin level. Life Sci.23, 1549–1556 (1978).
Fowler, C. L., Callingham, B. A., Mantle, T. J., Tipton, K. F. Monoamine oxidase A and B: a useful concept. Biochem. Pharmacol.27, 97–101 (1978).
Fuxe, K., Agnati, L., Tsuchiya, K., Hökfelt, T., Johansson, G., Lundbrink, P., Löfström, A., Ungerstedt, U. Effect of antipsychotic drugs on central catecholamine neurons of rat brain. In: Antipsychotic drugs, Pharmacodynamics and Pharmacokinetics (Sedvall, G., ed.), pp. 117 to 132. Oxford: Pergamon Press. 1975.
Gudelsky, G. A., Moore, K. E. Differential drug effects on dopamine concentrations and rates of turnover in the median eminence, olfactory tubercle and corpus striatum. J. Neural Transm.38, 95–105 (1976).
Gudelsky, G. A., Moore, K. E. A comparison of the effect of haloperidol on dopamine turnover in the striatum, olfactory tubercle and median eminence. J. Pharmacol. Exp. Ther.202, 149–156 (1977).
Herman, J. P., Fekete, M., Palkovits, M., Stark, E. Catecholamine turnover measurement and ACTH-induced short-term changes of catecholamine levels in individual brain nuclei. Pol. J. Pharmacol.29, 323–332 (1977).
Javoy, F., Hamon, M., Glowinski, J. Disposition of newly synthetized amines in cell bodies and terminals of central catecholaminergic neurons. I. Effect of amphetamine and thioproperazine on the metabolism of catecholamines in the caudate nucleus, substantia nigra and the ventromedial nucleus, of the hypothalamus. Europ. J. Pharmacol.10, 178–188 (1970).
Kebabian, J. W., Saavedra, J. M., Axelrod, J. A sensitive enzymatic radioisotopic assay for 3, 4-dihydroxyphenylacetic acid. J. Neurochem.28, 795–801 (1977).
Kizer, J. S., Kopin, I. J., Zivin, J. A.: Estimates of catecholamine turnover rates in individual hypothalamic nuclei of the rat by use of alpha-methyl-paratyrosine. Brit. J. Pharmacol.54, 243P (1975).
Kizer, J. S., Palkovits, M., Brownstein, M. J. The projections of the A8, A9 and A10 dopaminergic cell bodies: evidence for a nigral-hypo-thalamic-median eminence dopaminergic pathway. Brain Res.108, 363–370 (1976).
Korf, J., Zieleman, M., Westerink, H. C. Metabolism of dopamine in the substantia nigra after antidromic activation. Brain Res.120, 184–187 (1977).
Lowry, O., Rosebrough, N., Farr, A., Randall, R. Protein measurement with the Folin phenol reagent. J. biol. Chem.193, 265–275 (1951).
Nybäck, N. Effect of brain lesions and chlorpromazine on accumulation and disappearance of catecholamine formed in vivo from14C-tyrosine. Acta Physiol. Scand.84, 54–64 (1972).
Palkovits, M. Isolated removal of hypothalamic or other brain nuclei of the rat. Brain Res.59, 449–450 (1973).
Palkovits, M., Brownstein, M. J., Saavedra, J. M., Axelrod, J. Norepinephrine and dopamine content of hypothalamic nuclei of the rat. Brain Res.77, 137–149 (1974).
Roffler-Tarlov, S., Sharman, D. F., Tegerdine, P. 3, 4-Dihydroxyphenyacetic acid and 4-hydroxy-3-methoxyphenylacetic acid in the mouse striatum: A reflection of intra- and extraneuronal metabolism of dopamine. Brit. J. Pharmacol.42, 343–351 (1971).
Scatton, B., Thierry, A. M., Glowinski, J., Julou, L. Effects of thiproperazine and apomorphine on dopamine synthesis in the mesocortical dopaminergic systems. Brain Res.88, 389–393 (1975).
Spano, P. F., Neff, N. H. Metabolie fate of caudate nucleus dopamine. Brain Res.42, 139–145 (1972).
Tassin, J. P., Cheramy, A., Blanc, G., Thierry, A. M., Glowinski, J. Topographical distribution of dopaminergic innervation and of dopaminergic receptors in the striatum. I. Microestimation of (H3)dopamine uptake and dopamine content in microdiscs. Brain Res.107, 291–301 (1976).
Usdin, E., Bunney, W. E., jr. (eds.): Pre- and postsynaptic receptors. New York: Marcel Dekker Inc. 1975.
Van der Gugten, J., Palkovits, M., Wijnen, H. L. J. M., Versteeg, D. H. G. Regional distribution of adrenaline in rat brain. Brain Res.107, 171 to 175 (1976).
Versteeg, D. H. G., Van der Gugten, J., Van Ree, J. M. Regional turnover and synthesis of catecholamines in rat hypothalamus. Nature256, 502–503 (1975).
Waldmeier, P. C., Delini-Stule, A., Maitre, L. Preferential deamination of dopamine by an A type monoamine oxidase in rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol.292, 9–14 (1976).
Westerink, B. H. C., Lejeune, B., Korf, J., van Praag, H. M. On the significance of regional dopamine metabolism in the rat brain for the classification of centrally acting drugs. Europ. J. Pharmacol.42, 179 to 190 (1977).
Wiesel, F.-A., Fri, C.-G., Sedvall, G. Determination of homovanillic acid turnover in rat striatum using a monoamine oxidase inhibitor. Europ. J. Pharmacol.23, 104–106 (1973).
Wilk, S., Watson, E., Travis, B. Evaluation of dopamine metabolism in rat striatum by a gas Chromatographie technique. Europ. J. Pharmacol.30, 238–243 (1975).
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Fekete, M.I.K., Herman, J.P., Kanyicska, B. et al. Dopamine, noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) levels of individual brain nuclei, effects of haloperidol and pargyline. J. Neural Transmission 45, 207–218 (1979). https://doi.org/10.1007/BF01244409
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DOI: https://doi.org/10.1007/BF01244409