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Presynaptic regulation of electrically evoked dopamine overflow in nucleus accumbens: a pharmacological study using fast cyclic voltammetry in vitro

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Summary

Fast cyclic voltammetry has been used to measure electrically evoked dopamine overflow from slices of rat nucleus accumbens in vitro. The substance detected was shown voltammetrically and biochemically to be dopamine of neuronal origin. Enough dopamine was released by a single electrical pulse to be easily detectable, and under these conditions there was no auto-inhibition by the endogenous transmitter (as demonstrated by the failure of dopamine antagonists to increase the amount released). There was no significant inhibition, or enhancement, of release by agonists at the following receptor types: dopamine D1, 5-hydroxytryptamine, cholinoceptors, α1-, α2-, β-adrenoceptors, cholecystokinin or neurotensin receptors. However, the dopamine D2 receptor agonist, quinpirole, was capable of totally inhibiting the release; this effect was concentration-dependently antagonized by the D2 antagonists haloperidol, sulpiride, metoclopramide and clozapine, with potencies which corresponded to their affinities for D2 receptors in striatal tissue. The results show that the presynaptic receptors on dopaminergic nerve terminals are of the D2 type and apparently identical to those in the corpus striatum.

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References

  1. Agnati LF, Fuxe K, Benfanati F, Battistini N (1983) Neurotensin in vitro markedly reduced the affinity in subcortical limbic 3H-N-propylnorapomorphine binding sites. Acta Physiol Scand 119:459–461

  2. Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol Chemother 14:48–58

  3. Asano T, Lew JY, Goldstein HO (1980) Dopamine (DA) agonist activity of an ergoline pyrazole analog (LY141865). Fed Prog 39:615

  4. Bull DR, Sheehan MJ (1989) Dopamine release measured by fast cyclic voltammetry in nucleus accumbens slices. J Neurosci Method 29:299

  5. Bull DR, Palij P, Sheehan MJ, Millar J, Kruk ZL, Humphrey PPA (1990) The application of fast cyclic voltammetry to measurement of electrically evoked dopamine overflow from brain slices in vitro. J Neurosci Methods 32:37–44

  6. Carlsson A, Lindqvist M (1963) Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normethanephrine in mouse brain. Acta Pharmacol Toxicol 20: 140–144

  7. Carter DA, Fibiger HC (1977) Ascending projections of presumed dopamine containing neurons of the ventral tegmentum of the rat as demonstrated by horseradish peroxidase. Neuroscience 2:569–576

  8. Faedda G, Kula NS, Baldessarini RJ (1989) Pharmacology of binding of 3H-Sch-23390 to D-1 dopaminergic receptor sites in rat striatal tissue. Biochem Pharmacol 38:473–480

  9. Herdon H, Nahorski SR (1985) Comparison between radiolabelled and endogenous dopamine release from rat striatal slices: effects of electrical field stimulation and regulation by D2-autoreceptors. Naunyn-Schmiedeberg's Arch Pharmacol 335:238–242

  10. Hetey L, Drescher K (1986) Influence of antipsychotics on presynaptic receptors modulating the release of dopamine in synaptosomes of the nucleus accumbens of rats. Neuropharmacology 25:1103 -1109

  11. Hunt P, Raynard J-P, Leven M, Schacht U (1979) Dopamine uptake inhibitors and releasing agents differentiated by the use of synaptosomes and field-stimulated brain slices in vitro. Biochem Pharmacol 28:2011–2016

  12. Kelly E, Jenner P, Marsden CD (1985) Evidence that [3H]dopamine is taken up and released from nondopaminergic nerve terminals in the rat substantia nigra in vitro. J Neurochem 45:137–144

  13. Krivoy WA, Couch JR, Stewart JM, Zimmerman E (1980) Substance P as a synaptic modulator. In: Ajmone Marsan C, Traczyk WZ (eds) Neuropeptides and Neurotransmission. Raven Press, New York, pp 85–92

  14. Ljundberg T, Ungerstedt U (1978) Classification of neuroleptic drugs according to their ability to inhibit apomorphine-induced locomotion and gnawing; evidence for two different mechanisms of action. Psychopharmacologia 56:239–247

  15. Mathysse S (1974) Implications of catecholamine systems of the brain in schizophrenia. Res Publ Assoc Res New Merit Dis 53:305–315

  16. Matz R, Rich W, Oh D, Thompson H, Gershon S (1974) Clozapine — a potential antipsychotic agent without extrapyramidal manifestations. Curr Ther Res 14:687–695

  17. Meltzer HY, Matsubara S, Lee J (1989) Classification of typical and atypical antipsychotic drug on the basis of dopamine D-1 and D-2 and serotonin-2 pK i values. J Pharmacol Exp Ther 251:238

  18. Millar J, Stamford JA, Kruk ZL, Wightman RM (1985) Electrochemical pharmacological and electrophysiological evidence of rapid dopamine release and removal in the rat caudate nucleus following electrical stimulation of the median forebrain bundle. Eur J Pharmacol 109:341–348

  19. Nemeroff CB, Lutlinger D, Herrandez DE, Mailman RB, Mason GA, Davis SD, Widerlov E, Frye GD, Kilts CA, Beaumont K, Breese GR, Prange AJ (1983) Interactions of neurotensin with brain dopamine systems: Biochemical and behavioural studies. J Pharmacol Exp Ther 225:337–345

  20. Niemegeers CIE, Janssen PAJ (1979) A systematic review of the pharmacological activities of dopamine antagonists. Life Sci 24:2201–2216

  21. Palij P, Bull DR, Sheehan MJ, Humphrey PPA, Millar J, Stamford J, Kruk ZL (1989) A new technique for quantitative measurement of stimulated endogenous dopamine release in brain slices using voltammetry. Br J Pharmacol 94: P 347

  22. Palij P, Bull DR, Sheehan MJ, Millar J, Stamford J, Kruk ZL, Humphrey PPA (1990) Presynaptic regulation of dopamine release in corpue striatum monitored in vitro in real time by fast cyclic voltammetry. Brain Res 509:172–174

  23. Paxinos G, Watson C (1986) The rat brain in stereotaxic co-ordinates. Academic Press, London

  24. Quirion R (1983) Interactions between neurotensin and dopamine in the brain: an overview. Peptides 4:609–615

  25. Reyneke L, Russell VA, Taljaard JJF (1987) The modulatory effects of neurotensin on [3H]dopamine release from rat nucleus accumbens slices is enhanced after chronic desipramine treatment. Brain Res 425:114–119

  26. Robbins TW, Everitt BJ (1982) Functional studies of the central catecholamines. Int Rev Neurobiol 23:303–365

  27. Stamford JA, Kruk ZL, Millar J (1985) Ascorbic acid does not modulate stimulated dopamine release: in vivo voltammetric data in the rat. Neurosci Lett 60:357–362

  28. Starke K, Göthert M, Kilbinger H (1989) Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev 69:864–989

  29. Van der Zee P, Koger HS, Gootyes J, Hespe W (1980) Aryl-14-dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake. Eur J Med Chem 15:363–370

  30. Vickroy TW, Bianchi BR, Kerwin JF, Kopecka H, Nadzan AM (1988) Evidence that type A CCK receptors facilitate dopamine efflux in rat brain. Eur J Pharmacol 152:371–372

  31. Voigt MR, Wang RY (1983) In vivo release of dopamine in the nucleus accumbens of the rat: modulation by cholecystokinin. Brain Res 296:189–193

  32. White FJ, Wang RY (1983) Differential effects of classical and atypical antipsychotic drugs on A9 and A10 dopamine neurons. Science 221:1054–1057

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Correspondence to D. R. Bull.

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Bull, D.R., Sheehan, M.J. Presynaptic regulation of electrically evoked dopamine overflow in nucleus accumbens: a pharmacological study using fast cyclic voltammetry in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 343, 260–265 (1991). https://doi.org/10.1007/BF00251124

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Key words

  • Voltammetry
  • Brain slice
  • Dopamine release
  • D2-receptors
  • Nucleus accumbens