Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1980 Jun;69(2):241–247. doi: 10.1111/j.1476-5381.1980.tb07896.x

3,4-dihydroxyphenylacetic acid (DOPAC) and the rat mesolimbic dopaminergic pathway: drug effects and evidence for somatodendritic mechanisms.

P M Beart, A L Gundlach
PMCID: PMC2044258  PMID: 6108139

Abstract

1 Drug effects on dopamine catabolism of the mesolimbic dopaminergic pathway have been investigated using a sensitive radioenzymatic assay for 3,4-dihydroxyphenylacetic acid (DOPAC). 2 Turnover of DOPAC was less rapid in the ventral tegmentum (containing somata and dendrites) than in the nucleus accumbens (containing nerve terminals): 9 and 115 ng g-1 min-1 for ventral tegmentum and nucleus accumbens respectively. 3 Reserpine (5 mg/kg, 1 h) elevated DOPAC concentration to a greater extent in ventral tegmentum than in nucleus accumbens. 4 Neuroleptic drugs elevated DOPAC levels in ventral tegmentum and nucleus accumbens. Thioridazine, sulpiride and clozapine, thought to act preferentially on the mesolimbic system, caused a similar elevation in both brain regions. 5 gamma-Butyrolactone (750 mg/kg) caused a significant decrease in the DOPAC concentration in ventral tegmentum after 0.5 and 1 h, while DOPAC levels in nucleus accumbens were not significantly altered at these time intervals. 6 Similarities exist between the dopamine catabolism in somatodendritic and nerve terminal regions of mesolimbic dopaminergic neurones in the response to neuroleptic drugs, but differences in catabolism are evident following certain pharmacological treatments such as reserpine and gamma-butyrolactone. 7 Dopamine release occurs in the somatodendritic region of mesolimbic dopaminergic neurones and release sites may be dendritic as has been found for nigrostriatal dopaminergic neurones.

Full text

PDF
241

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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. 1977 Sep;29(3):599–601. doi: 10.1111/j.1471-4159.1977.tb10711.x. [DOI] [PubMed] [Google Scholar]
  2. Bartholini G. Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. J Pharm Pharmacol. 1976 May;28(5):429–433. doi: 10.1111/j.2042-7158.1976.tb04648.x. [DOI] [PubMed] [Google Scholar]
  3. Björklund A., Lindvall O. Dopamine in dendrites of substantia nigra neurons: suggestions for a role in dendritic terminals. Brain Res. 1975 Jan 17;83(3):531–537. doi: 10.1016/0006-8993(75)90849-5. [DOI] [PubMed] [Google Scholar]
  4. Carter D. A., Fibiger H. C. Ascending projections of presumed dopamine-containing neurons in the ventral tegmentum of the rat as demonstrated by horseradish peroxidase. Neuroscience. 1977;2(4):569–576. doi: 10.1016/0306-4522(77)90052-5. [DOI] [PubMed] [Google Scholar]
  5. Colpaert F. C., Van Bever W. F., Leysen J. E. Apomorphine: chemistry, pharmacology, biochemistry. Int Rev Neurobiol. 1976;19:225–268. doi: 10.1016/s0074-7742(08)60705-9. [DOI] [PubMed] [Google Scholar]
  6. Da Prada M., Zürcher Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci. 1976 Oct 15;19(8):1161–1174. doi: 10.1016/0024-3205(76)90251-4. [DOI] [PubMed] [Google Scholar]
  7. Geffen L. B., Jessell T. M., Cuello A. C., Iversen L. L. Release of dopamine from dendrites in rat substantia nigra. Nature. 1976 Mar 18;260(5548):258–260. doi: 10.1038/260258a0. [DOI] [PubMed] [Google Scholar]
  8. Glowinski J., Iversen L. L. Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem. 1966 Aug;13(8):655–669. doi: 10.1111/j.1471-4159.1966.tb09873.x. [DOI] [PubMed] [Google Scholar]
  9. Hefti F., Lienhart R., Lichtensteiger W. Transmitter metabolism in substantia nigra after inhibition of dopaminergic neurones by butyrolactone. Nature. 1976 Sep 23;263(5575):341–343. doi: 10.1038/263341a0. [DOI] [PubMed] [Google Scholar]
  10. Horn A. S., Cuello A. C., Miller R. J. Dopamine in the mesolimbic system of the rat brain: endogenous levels and the effects of drugs on the uptake mechanism and stimulation of adenylate cyclase activity. J Neurochem. 1974 Feb;22(2):265–270. doi: 10.1111/j.1471-4159.1974.tb11589.x. [DOI] [PubMed] [Google Scholar]
  11. Iversen L. L. Dopamine receptors in the brain. Science. 1975 Jun 13;188(4193):1084–1089. doi: 10.1126/science.2976. [DOI] [PubMed] [Google Scholar]
  12. Karoum F., Neff N. H., Wyatt R. J. The dynamics of dopamine metabolism in various regions of rat brain. Eur J Pharmacol. 1977 Aug 15;44(4):311–318. doi: 10.1016/0014-2999(77)90304-1. [DOI] [PubMed] [Google Scholar]
  13. Kelly P. H., Moore K. E. Mesolimbic dopaminergic neurones in the rotational model of nigrostriatal function. Nature. 1976 Oct 21;263(5579):695–696. doi: 10.1038/263695a0. [DOI] [PubMed] [Google Scholar]
  14. Korf J., Zieleman M., Westerink B. H. Dopamine release in substantia nigra? Nature. 1976 Mar 18;260(5548):257–258. doi: 10.1038/260257a0. [DOI] [PubMed] [Google Scholar]
  15. Matthysse S. Antipsychotic drug actions: a clue to the neuropathology of schizophrenia? Fed Proc. 1973 Feb;32(2):200–205. [PubMed] [Google Scholar]
  16. McGeer E. G., Parkinson J., McGeer P. L. Neonatal enzymic development in the interpeduncular nucleus and surrounding ventral tegmentum. Exp Neurol. 1976 Oct;53(1):109–114. doi: 10.1016/0014-4886(76)90286-7. [DOI] [PubMed] [Google Scholar]
  17. Murphy G. F., Robinson D., Sharman D. F. The effect of tropolone on the formation of 3,4-dihydroxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetic acid in the brain of the mouse. Br J Pharmacol. 1969 May;36(1):107–115. doi: 10.1111/j.1476-5381.1969.tb08308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pijnenburg A. J., Honig W. M., Van Rossum J. M. Inhibition of d-amphetamine-induced locomotor activity by injection of haloperidol into the nucleus accumbens of the rat. Psychopharmacologia. 1975;41(2):87–95. doi: 10.1007/BF00421062. [DOI] [PubMed] [Google Scholar]
  19. Roth R. H., Murrin L. C., Walters J. R. Central dopaminergic neurons: effects of alterations in impulse flow on the accumulation of dihydroxyphenylacetic acid. Eur J Pharmacol. 1976 Mar;36(1):163–171. doi: 10.1016/0014-2999(76)90268-5. [DOI] [PubMed] [Google Scholar]
  20. Stevens J. R. An anatomy of schizophrenia? Arch Gen Psychiatry. 1973 Aug;29(2):177–189. doi: 10.1001/archpsyc.1973.04200020023003. [DOI] [PubMed] [Google Scholar]
  21. Walters J. R., Roth R. H. Effect of gamma-hydroxybutyrate on dopamine and dopamine metabolites in the rat striatum. Biochem Pharmacol. 1972 Aug 1;21(15):2111–2121. doi: 10.1016/0006-2952(72)90164-5. [DOI] [PubMed] [Google Scholar]
  22. Westerink B. H., Korf J. Comparison of effects of drugs on dopamine metabolism in the substantia nigra and the corpus striatum of rat brain. Eur J Pharmacol. 1976 Nov;40(1):131–136. doi: 10.1016/0014-2999(76)90362-9. [DOI] [PubMed] [Google Scholar]
  23. Westerink B. H., Korf J. Determination of nanogram amounts of homovanillic acid in the central nervous system with a rapid semiautomated fluorometric method. Biochem Med. 1975 Feb;12(2):106–115. doi: 10.1016/0006-2944(75)90101-5. [DOI] [PubMed] [Google Scholar]
  24. Westerink B. H., Korf J. Turnover of acid dopamine metabolites in striatal and mesolimbic tissue of the rat brain. Eur J Pharmacol. 1976 Jun;37(2):249–255. doi: 10.1016/0014-2999(76)90032-7. [DOI] [PubMed] [Google Scholar]
  25. Wilson C. J., Groves P. M., Fifková E. Monoaminergic synapses, including dendro-dendritic synapses in the rat substantia nigra. Exp Brain Res. 1977 Nov 24;30(2-3):161–174. doi: 10.1007/BF00237248. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES