Histamine inhibits dopamine release in the mouse striatum via presynaptic H3 receptors

  • E. Schlicker
  • K. Fink
  • M. Detzner
  • M. Göthert
Full Papers


In superfused mouse striatal slices preincubated with [3H] dopamine 25 nmol/l, the electrically (3 Hz) evoked tritium overflow was inhibited by histamine 10 μmol/l by 18%. The degree of inhibition was increased to 38% by haloperidol but not affected by (1) atropine, (2) reducing the stimulation frequency to 0.3 Hz or (3) increasing the concentration of [3H]dopamine (used for preincubation) to 100 nmol/l. The effect of histamine was mimicked by the H3 agonist R-(−)-α-methylhistamine; it was not affected by the H1 antagonist dimetindene and the H2 antagonist ranitidine but abolished by the H3 antagonist thioperamide. Tritium overflow evoked by Ca2+ ions (introduced into Ca2+free, K+-rich medium containing tetrodotoxin) was not affected by histamine 10 μmol/l in the absence, but inhibited (by 30%) in the presence of haloperidol; the effect of histamine was abolished by thioperamide. In conclusion, the dopaminergic nerve terminals in the mouse striatum are endowed with presynaptic H3 receptors. Simultaneous blockade of dopamine autoreceptors increases the extent of the H3 receptor-mediated inhibition of dopamine release.


Presynaptic H3 receptors dopamine release mouse striatal slices thioperamide R-(−)-α-Methylhistamine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arrang J-M, Garbarg M, Schwartz J-C (1983) Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 302: 832–837Google Scholar
  2. Arrang J-M, Garbarg M, Lancelot JC, Lecomte JM, Pollard H, Robba M, Schunack W, Schwartz J-C (1987) Highly potent and selective ligands for histamine H3 receptors. Nature 327: 117–123Google Scholar
  3. Clapham J, Kilpatrick GJ (1992) Histamine H3 receptors modulate the release of [3H]-acetylcholine from slices of rat entorhinal cortex: evidence for the possible existence of H3 receptor subtypes. Br J Pharmacol 107: 919–923Google Scholar
  4. Fink K, Schlicker E, Neise A, Göthert M (1990) Involvement of presynaptic H3 receptors in the inhibitory effect of histamine on serotonin release in the rat brain cortex. Naunyn Schmiedebergs Arch Pharmacol 342: 513–519Google Scholar
  5. Hill SJ (1990) Distribution, properties, and functional characteristics of three classes of histamine receptor. Pharmacol Rev 42: 45–83Google Scholar
  6. Hoffmann IS, Talmaciu RK, Ferro CP, Cubeddu LX (1988) Sustained high release at rapid stimulation rates and reduced functional autoreceptors characterize prefrontal cortex dopamine terminals. J Pharmacol Exp Ther 245: 761–772Google Scholar
  7. Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Statist 6: 65–70Google Scholar
  8. Langer SZ, Lehmann J (1988) Presynaptic receptors on catecholamine neurones. In: Trendelenburg U, Weiner N (eds) Handbook of experimental pharmacology, vol 90/I. Springer, Berlin Heidelberg New York Tokyo, pp 419–507Google Scholar
  9. Lümmen G, Schlicker E (1991) Presynaptic histamine H3 receptors on the noradrenergic neurones in the rat brain: investigations into signal transduction and interaction with α2-autoreceptors. Naunyn Schmiedebergs Arch Pharmacol 343 [Suppl]: R 94Google Scholar
  10. Schlicker E, Betz R, Göthert M (1988) Histamine H3 receptor-mediated inhibition of serotonin release in the rat brain cortex. Naunyn Schmiedebergs Arch Pharmacol 337: 588–590Google Scholar
  11. Schlicker E, Fink K, Hinterthaner M, Göthert M (1989) Inhibition of noradrenaline release in the rat brain cortex via presynaptic H3 receptors. Naunyn Schmiedebergs Arch Pharmacol 340: 633–638Google Scholar
  12. Schlicker E, Glaser T, Lümmen G, Neise A, Göthert M (1991) Serotonin and histamine receptor-mediated inhibition of serotonin and noradrenaline release in rat brain cortex under nimodipine treatment. Neurochem Int 19: 437–444Google Scholar
  13. Schlicker E, Behling A, Liimmen G, Göthert M (1992a) Histamine H3A receptor-mediated inhibition of noradrenaline release in the mouse brain cortex. Naunyn Schmiedebergs Arch Pharmacol 345: 489–493Google Scholar
  14. Schlicker E, Lümmen G, Behling A, Göthert M (1992b) Inhibition of noradrenaline release via NEM-sensitive H3 receptors in the mouse brain cortex: more marked effect than in the rat brain. Agents Actions (Special Conference Issue): C339–C 342Google Scholar
  15. Schlicker E, Behling A, Lümmen G, Malinowska B, Göthert M (1992c) Mutual interaction of histamine H3 receptors and α2-adrenoceptors on noradrenergic terminals in mouse and rat brain cortex. Naunyn Schmiedebergs Arch Pharmacol 345: 639–646Google Scholar
  16. Schwartz J-C, Arrang J-M, Garbarg M, Pollard H, Ruat M (1991) Histaminergic transmission in the mammalian brain. Physiol Rev 71: 1–51Google Scholar
  17. Smits RPJM, Mulder AH (1991) Inhibitory effects of histamine on the release of serotonin and noradrenaline from rat brain slices. Neurochem Int 18: 215–220Google Scholar
  18. Starke K, Göthert M, Kilbinger H (1989) Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev 69: 864–989Google Scholar
  19. Timmerman H (1990) Histamine H3 ligands: just pharmacological tools or potential therapeutic agents? J Med Chem 33: 4–10Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • E. Schlicker
    • 1
  • K. Fink
    • 1
  • M. Detzner
    • 1
  • M. Göthert
    • 1
  1. 1.Institut für Pharmakologie und ToxikologieRheinische Friedrich-Wilhelms-UniversitätBonnFederal Republic of Germany

Personalised recommendations