Agonist and antagonist actions of lisuride on dopamine neurons: electrophysiological evidence

  • G. L. Gessa
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 27)


The effect of lisuride (LIS) on the firing rate of A 9 dopamine (DA) neurons in chloral-hydrate anesthetized and unanesthetized (paralyzed) rats was compared. In both preparations, the microiontophoretic application of LIS onto DA cell bodies consistently inhibited the electrical activity of the neurons. On the other hand, the effect of intravenous LIS differed in the two preparations. In anesthetized rats LIS (10–100 µg/kg) inhibited in a dose-related manner the firing rate of most DA neurons tested, whereas in unanesthetized rats LIS produced a dose-related increase in firing rate. The latter effect was transient, subsiding within 5 min, and was followed by the return of firing rate to baseline or slightly below it. Irrespective of the animal preparation, after the initial effect of LIS had subsided, DA neurons became totally insensitive to additional doses of LIS, to apomorphine and haloperidol. Such an insensitivity of DA neurons was present 1 to 6 but not 24 h after LIS (0.2mg/kg, subcutaneously) treatment. A hypothesis is proposed to explain the different effects of LIS.


Firing Rate Dopamine Agonist Dopamine Neuron Antagonist Action DAergic Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bannon HJ, Grace AA, Bunney BS, Roth RH (1980) Evidence for an irreversible interaction of bromocryptine with central dopamine receptors. Naunyn Schmiedebergs Arch Pharmacol 312: 37–41PubMedCrossRefGoogle Scholar
  2. Chiodo LA, Bunney BS (1984) Effects of dopamine antagonists on midbrain dopamine cell activity. In: Usdin E, Carlsson A, Dahlstrom A, Engel J (eds) Catecholamines: neuropharmacology and central nervous system - theoretical aspects. A R Liss, New York, pp 369–391Google Scholar
  3. Calne DB, Horowski R, McDonald RJ, Wuttke W (1983) Lisuride and other dopamine agonists. Raven Press, New YorkGoogle Scholar
  4. Clark D, Hjorth S, Carlsson A (1985) Dopamine-receptor agonists: mechanisms underlying autoreceptor selectivity I. Review of the evidence. J Neural Transm 62: 1–52Google Scholar
  5. Gessa GL, Westfall TC, Boi V, Mereu GP (1986 b) Mixed dopamine agonist and antagonist properties of lisuride. Federation Proceedings, 70th annual meeting. Abstract 1623, vol 45 /3. p433Google Scholar
  6. Gessa GL, Yoon K-WP, Boi V, Westfall TC, Mereu G (1986 a) Different anesthesia preparations reveal appropriate responses of dopamine mid-brain neurons to dopamine agonist and antagonist drugs. Soc Neurosci Ann Meeting. Abstract 133.17, vol 12/1. p486Google Scholar
  7. Gopinathan G, Colne DB (1981) Actions of ergot derivatives in parkinsonism. In: Rose FC, Capildeo R (eds) Research progress in Parkinson’s disease. Pitman Medical, New York, pp 324–332Google Scholar
  8. Gudrun HM, Paalzow LK (1986) L-dopa: how it may exacerbate parkinsonian symptoms. Trends Pharmacol Sci 7: 15–19CrossRefGoogle Scholar
  9. Horowski R (1978) Differences in the dopaminergic effects of the ergot derivatives bromo-criptine, lisuride, and d-LSD as compared with apomorphine. Eur J Pharmacol 51: 157–166PubMedCrossRefGoogle Scholar
  10. Kehr W (1984) Transdihydrolisuride, a partial dopamine receptor antagonist: effects on monoamine metabolism. Eur J Pharmacol 97: 111–119PubMedCrossRefGoogle Scholar
  11. Krejci I, Schuh J, Pragerova H, Dlabac A (1985) Lisuride and transdihydolisuride: differences in action on central dopaminergic functions in dependence on the location and the state of receptors. Pol J Pharmacol Pharm 37: 263–271PubMedCrossRefGoogle Scholar
  12. Lieberman AN, Goldstein M, Gopinathan G, Neophytides A, Leibwitz M, Walker R, Hiesiger E (1983) Lisuride in Parkinson’s disease and related disorder. In: Calne DB, McDonald RJ, Horowski R, Wuttke W (eds) Lisuride and other dopamine agonists. Raven Press, New York, pp 419–430Google Scholar
  13. Llinas R, Greenfield SA, Jahnsen H (1984) Electrophysiology of pars compacta cells in the in vitro substantia nigra: a possible mechanism for dendritic release. Brain Res 294: 127–132PubMedCrossRefGoogle Scholar
  14. Mereu GP (1982) Activation of dopaminergic neurons by sulpiride. In: Biggio G, Costa E, Gessa GL, Spano PF (eds) Receptors as supramolecular entities, vol 1. Pergamon Press, New York, pp 147–153Google Scholar
  15. Mereu GP, Fanni B, Gessa GL (1984) General anesthetics prevent dopaminergic neuron stimulation by neuroleptics. In: Usdin E, Carlsson A, Dahlstrom A, Engel J (eds) Catecholamines: neuropharmacology and central nervous system-theoretical aspects. Neurobiology, vol8B. A R Liss, New York, pp 353–358Google Scholar
  16. Mereu G, Muntoni F, Collu M, Boi V, Gessa GL (1986 a) Delayed blockade of dopamine autoreceptors by lisuride. In: Biggio G, Costa E (eds) Dopamine receptors physiology. Liviana Press, Padova Fidia Research Series, vol 3, pp 599–601Google Scholar
  17. Mereu G, Muntoni F, Romani F, Calabresi P, Boi V, Gessa GL (1986 b) Responsiveness to “autoreceptor” doses of apomorphine is inversely correlated with the firing rate of dopaminergic neurons. Neurosci Lett 65: 161–166Google Scholar
  18. Mereu G, Hu XT, Wang RY, Westfall TC, Gessa GL (1986 c) Failure of subchronic lisuride to modify A 10 dopamine autoreceptors sensitivity. Brain Res 408: 210–214Google Scholar
  19. Rinne UK (1986) The importance of an early combination of a dopamine agonist and levodopa in the treatment of Parkinson’s disease. In: van Maanen J, Rinne UK (eds) Lisuride: a new dopamine agonist and Parkinson’s disease. Proceedings of a symposium held in Berlin. Excerpta Medica, Amsterdam, pp 64–71Google Scholar
  20. Rogawski MA, Aghajanian GK (1979) Response of central monoaminergic neurons to lisuride: comparison with LSD. Life Sei 24: 1289–1298CrossRefGoogle Scholar
  21. Seeman P (1981) Brain dopamine receptors. Pharmacol Rev 32: 229–313Google Scholar
  22. Skirboll LR, Grace A A, Bunney BS (1979) Dopamine auto- and postsynaptic receptors: electrophysiological evidence for differential sensitivity to dopamine agonists. Science 206: 80–82PubMedCrossRefGoogle Scholar
  23. Stoof JC, Kebabian JW (1984) Two dopamine receptors: biochemistry, physiology and pharmacology. Life Sei 35: 2281–2296CrossRefGoogle Scholar
  24. Tissari AH, Gessa GL (1983) Ergot-induced inhibition of dopamine synthesis in striatal synaptosomes: a D-2 DA receptor-mediated mechanism. In: Calne DB etal (eds) Lisuride and other dopamine agonists. Raven Press, New York, pp 33–34Google Scholar
  25. Traub M, Wagner HR, Hassan M, Jackson-Lewis V, Fahn S (1985) The effects of chronic bromocriptine treatment on behaviour and dopamine receptor binding in the rat striatum. Eur J Pharmacol 118: 147–154PubMedCrossRefGoogle Scholar
  26. Walters JR, Baring MD, Lakoski JM (1979) Effects of ergolines on dopaminergic and serotoninergic single unit activity. In: Fuxe K, Calne DB (eds) Dopaminergic ergot derivatives and motor function. Pergamon Press, New York, pp 207–221CrossRefGoogle Scholar
  27. Walters JR, Baring MD, Carlsson JH (1986) Effects of D-l and D-2 receptor stimulation on single unit activity in substantia nigra and globus pallidus. In: Woodruff GN (ed) Dopamine systems and their regulation. Macmillan Press, London, pp 63–78Google Scholar
  28. White FJ, Wang RY (1983) Comparison of the effects of LSD and lisuride on A 10 dopamine neurons in the rat. Neuropharmacology 22: 669–676PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • G. L. Gessa
    • 1
  1. 1.Department of NeurosciencesUniversity of CagliariCagliariItaly

Personalised recommendations