Effects of neuroleptics on release of 3H-dopamine from slices of rat corpus striatum

  • Key Dismukes
  • Arie H. Mulder


The characteristics of 3H-DA release from striatal slices by electrical stimulation were analyzed and the effects of a number of neuroleptics thereon were examined under different experimental conditions. The butyrophenones, haloperidol and spiroperidol, already at low concentrations (0.1–1 μM) increased basal tritium efflux in a dose-dependent manner. The phenothiazines, chlorpromazine and fluphenazine, were much less effective in this respect.

The butyrophenones strongly inhibited the electrically stimulated overflow of both 3H-DA and 14C-GABA, while the phenothiazines again had little effect. The action of 1 μM haloperidol on 3H-DA release could be blocked by 10 μM cocaine, but not with 1 μM apomorphine. Apomorphine itself had no significant effect on 3H-DA release.

Our data do not support the suggestion that presynaptic DA receptors on dopaminergic nerve terminals may modulate the release of newly taken-up 3H-DA. Some neuroleptics, particularly the butyrophenones may have presynaptic effects not related to interaction with DA receptors. It is suggested that different mechanisms may be involved in the local presynaptic receptor-mediated feedback regulation of transmitter release in noradrenergic and dopaminergic systems in the CNS.

Key words

DA-release Neuroleptics Striatum slices GABA release Presynaptic DA receptors 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Cubeddu, L. X., Barnes, E., Langer, S. Z., Weiner, N.: Release of norepinephrine and dopamine-β-hydroxylase by nerve stimulation. I. Role of neuronal and extraneuronal uptake and of alpha presynaptic receptors. J. Pharmacol. exp. Ther. 190, 431–450 (1974)Google Scholar
  2. Dismukes, R. K., Mulder, A. H.: Cyclic AMP and α-receptor mediated modulation of noradrenaline release from rat brain slices. Europ. J Pharmacol. 39, 383–388 (1976)Google Scholar
  3. Farnebo, L. O., Hamberger, B.: Drug-induced release of 3H-monoamines from field-stimulated rat brain slices. Acta physiol. scand., Suppl. 371, 35–44 (1971)Google Scholar
  4. Farnebo, L. O., Hamberger, B.: Catecholamine release and receptors in brain slices. In: Frontiers in catecholamine research (E. Usdin, and S. H. Snyder, eds.), pp. 589–593. New York: Pergamon Press 1973Google Scholar
  5. Häggendal, J.: Regulation of catecholamine release. In: Frontiers in catecholamine research (E. Usdin and S. H. Snyder, eds.), pp. 531–535. New York: Pergamon Press 1973Google Scholar
  6. Hedqvist, P.: Role of the α-receptor in the control of noradrenaline release from sympathetic nerves. Acta physiol. scand. 90, 158–165 (1974)Google Scholar
  7. Iversen, L. L., Rogawski, M. A., Miller, R. J.: Comparison of the effects of neuroleptic drugs on pre-and postsynaptic dopaminergic mechanisms in the rat striatum. Molec. Pharmacol. 12, 251–262 (1976)Google Scholar
  8. Kehr, W.: A method for the isolation and determination of 3-methoxytyramine in brain tissue. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 149–158 (1974)Google Scholar
  9. Kirpekar, S. M., Furchgott, R. F., Wakade, A. R., Prat, J. C.: Inhibition by sympathomimetic amines of the release of norepinephrine evoked by nerve stimulation in the cat spleen. J. Pharmacol. exp. Ther. 187, 529–538 (1973)Google Scholar
  10. Mulder, A. H., Van den Berg, W. B., Stoof, J. C.: Calcium-dependent release of radiolabeled catecholamines and serotonin from rat brain synaptosomes in a superfusion system. Brain Res. 99, 419–424 (1975)Google Scholar
  11. Ross, S. B., Rényi, A. L.: Inhibition of the uptake of 3H-dopamine and 14C-5-hydroxytryptamine in mouse striatum slices. Acta pharmacol. (Kbh.) 36, 45–66 (1975)Google Scholar
  12. Seeman, P., Lee, T.: The dopamine releasing actions of neuroleptics and ethanol. J. Pharmacol. exp. Ther. 190, 131–140 (1974)Google Scholar
  13. Seeman, P., Lee, T.: Anti-psychotic drugs: Direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188, 1217–1219 (1975)Google Scholar
  14. Starke, K., Montel, H.: Alpha-receptor modulation of transmitter release from central noradrenergic neurones. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 53–60 (1973)Google Scholar
  15. Starke, K., Montel, H.: Influence of drugs with affinity for α-adrenoceptors on noradrenaline release by potassium, tyramine and dimethylphenylpiperazinium. Europ. J. Pharmacol. 27, 273–280 (1974)Google Scholar
  16. Stjärne, L.: Selectivity for catecholamines of presynaptic alpha receptors involved in feedback control of sympathetic neurotransmitter secretion in guinea-pig vas deferens. Naunyn-Schmiedeberg's Arch. Pharmacol. 288, 295–303 (1975)Google Scholar
  17. Stoof, J. C., Schipper, J., Mulder, A. H.: On the specificity and mechanism of action of m-tyrosine in antagonizing the central effects of reserpine in rats. Neuropharmacology 15, 379–382 (1976)Google Scholar
  18. Westfall, T. C., Besson, M. J., Giorguieff, M. F., Glowinski, J.: The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 279–287 (1976)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • Key Dismukes
    • 1
  • Arie H. Mulder
    • 1
  1. 1.Department of PharmacologyFree University, Medical FacultyAmsterdamThe Netherlands

Personalised recommendations