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. 1989 Sep;98(1):127–134. doi: 10.1111/j.1476-5381.1989.tb16872.x

The mechanism of amphetamine-induced inhibition of rat substantia nigra compacta neurones investigated with intracellular recording in vitro.

N B Mercuri 1, P Calabresi 1, G Bernardi 1
PMCID: PMC1854659  PMID: 2804542

Abstract

1. The effects of (+)-amphetamine (1-300 microM) applied by superfusion, on substantia nigra zona compacta neurones were studied in slices of the rat mesencephalon with intracellular recording techniques (current and voltage clamp mode). 2. Amphetamine inhibited the action potential discharge, hyperpolarized the cells and increased the membrane conductance. Under voltage clamp it produced an outward current. 3. The amphetamine outward current reversed at potentials negative to -100 mV (2.5 mM extracellular potassium) and was reduced by barium, (1 mM) suggesting an increased potassium conductance. 4. In slices treated with tetrodotoxin and calcium-free solution and added cobalt, amphetamine was still effective. 5. (-)-Sulpiride, (1 microM) a D2 antagonist, blocked the effects of both amphetamine and dopamine. 6. In slices treated for more than 3 h with 30 microM alpha-methyl-DL-tyrosine, an agent known to block the synthesis of dopamine, the action of amphetamine was attenuated, while dopamine was still effective. 7. Responses to applied dopamine were potentiated by cocaine (10 microM) but unaffected by amphetamine (1-3 microM). 8. It is suggested that the inhibition of substantia nigra compacta neurones by amphetamine is mainly due to the release of endogenous dopamine.

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Selected References

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  1. Aghajanian G. K., Bunney B. S. Dopamine"autoreceptors": pharmacological characterization by microiontophoretic single cell recording studies. Naunyn Schmiedebergs Arch Pharmacol. 1977 Mar;297(1):1–7. doi: 10.1007/BF00508803. [DOI] [PubMed] [Google Scholar]
  2. BEAMISH P., KILOH L. G. Psychoses due to amphetamine consumption. J Ment Sci. 1960 Jan;106:337–343. doi: 10.1192/bjp.106.442.337. [DOI] [PubMed] [Google Scholar]
  3. Browder S., German D. C., Shore P. A. Midbrain dopamine neurons: differential responses to amphetamine isomers. Brain Res. 1981 Mar 2;207(2):333–342. doi: 10.1016/0006-8993(81)90368-1. [DOI] [PubMed] [Google Scholar]
  4. Bunney B. S., Achajanian G. K. d-Amphetamine-induced inhibition of central dopaminergic neurons: mediation by a striato-nigral feedback pathway. Science. 1976 Apr 23;192(4237):391–393. doi: 10.1126/science.1257777. [DOI] [PubMed] [Google Scholar]
  5. Bunney B. S., Aghajanian G. K., Roth R. H. Comparison of effects of L-dopa, amphetamine and apomorphine on firing rate of rat dopaminergic neurones. Nat New Biol. 1973 Sep 26;245(143):123–125. doi: 10.1038/newbio245123a0. [DOI] [PubMed] [Google Scholar]
  6. Bunney B. S., Walters J. R., Roth R. H., Aghajanian G. K. Dopaminergic neurons: effect of antipsychotic drugs and amphetamine on single cell activity. J Pharmacol Exp Ther. 1973 Jun;185(3):560–571. [PubMed] [Google Scholar]
  7. Cheramy A., Leviel V., Glowinski J. Dendritic release of dopamine in the substantia nigra. Nature. 1981 Feb 12;289(5798):537–542. doi: 10.1038/289537a0. [DOI] [PubMed] [Google Scholar]
  8. Chiueh C. C., Moore K. E. D-amphetamine-induced release of "newly synthesized" and "stored" dopamine from the caudate nucleus in vivo. J Pharmacol Exp Ther. 1975 Mar;192(3):642–653. [PubMed] [Google Scholar]
  9. Costa E., Groppetti A., Naimzada M. K. Effects of amphetamine on the turnover rate of brain catecholamines and motor activity. Br J Pharmacol. 1972 Apr;44(4):742–751. doi: 10.1111/j.1476-5381.1972.tb07312.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Enna S. J., Dorris R. L., Shore P. A. Specific inhibition by -methyltyrosine of amphetamine-induced amine release from brain. J Pharmacol Exp Ther. 1973 Mar;184(3):576–582. [PubMed] [Google Scholar]
  11. GLOWINSKI J., AXELROD J. EFFECT OF DRUGS ON THE UPTAKE, RELEASE, AND METABOLISM OF H3-NOREPINEPHRINE IN THE RAT BRAIN. J Pharmacol Exp Ther. 1965 Jul;149:43–49. [PubMed] [Google Scholar]
  12. 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]
  13. Groves P. M., Wilson C. J., Young S. J., Rebec G. V. Self-inhibition by dopaminergic neurons. Science. 1975 Nov 7;190(4214):522–528. doi: 10.1126/science.242074. [DOI] [PubMed] [Google Scholar]
  14. Heikkila R. E., Orlansky H., Cohen G. Studies on the distinction between uptake inhibition and release of (3H)dopamine in rat brain tissue slices. Biochem Pharmacol. 1975 Apr 15;24(8):847–852. doi: 10.1016/0006-2952(75)90152-5. [DOI] [PubMed] [Google Scholar]
  15. Heikkila R. E., Orlansky H., Mytilineou C., Cohen G. Amphetamine: evaluation of d- and l-isomers as releasing agents and uptake inhibitors for 3H-dopamine and 3H-norepinephrine in slices of rat neostriatum and cerebral cortex. J Pharmacol Exp Ther. 1975 Jul;194(1):47–56. [PubMed] [Google Scholar]
  16. Kamal L. A., Arbilla S., Langer S. Z. Presynaptic modulation of the release of dopamine from the rabbit caudate nucleus: differences between electrical stimulation, amphetamine and tyramine. J Pharmacol Exp Ther. 1981 Mar;216(3):592–598. [PubMed] [Google Scholar]
  17. Lacey M. G., Mercuri N. B., North R. A. Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta. J Physiol. 1987 Nov;392:397–416. doi: 10.1113/jphysiol.1987.sp016787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lacey M. G., Mercuri N. B., North R. A. On the potassium conductance increase activated by GABAB and dopamine D2 receptors in rat substantia nigra neurones. J Physiol. 1988 Jul;401:437–453. doi: 10.1113/jphysiol.1988.sp017171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Meyerhoff J. L., Kant G. J. Release of endogenous dopamine from corpus striatum. Life Sci. 1978 Oct 9;23(14):1481–1486. doi: 10.1016/0024-3205(78)90129-7. [DOI] [PubMed] [Google Scholar]
  20. Nedergaard S., Hopkins C., Greenfield S. A. Do nigro-striatal neurones possess a discrete dendritic modulatory mechanism? Electrophysiological evidence from the actions of amphetamine in brain slices. Exp Brain Res. 1988;69(2):444–448. doi: 10.1007/BF00247591. [DOI] [PubMed] [Google Scholar]
  21. Nieoullon A., Cheramy A., Glowinski J. Release of dopamine in vivo from cat substantia nigra. Nature. 1977 Mar 24;266(5600):375–377. doi: 10.1038/266375a0. [DOI] [PubMed] [Google Scholar]
  22. Paden C., Wilson C. J., Groves P. M. Amphetamine-induced release of dopamine from the substantia nigra in vitro. Life Sci. 1976 Nov 15;19(10):1499–1506. doi: 10.1016/0024-3205(76)90094-1. [DOI] [PubMed] [Google Scholar]
  23. Pinnock R. D. Sensitivity of compacta neurones in the rat substantia nigra slice to dopamine agonists. Eur J Pharmacol. 1983 Dec 23;96(3-4):269–276. doi: 10.1016/0014-2999(83)90316-3. [DOI] [PubMed] [Google Scholar]
  24. Pinnock R. D. The actions of antipsychotic drugs on dopamine receptors in the rat substantia nigra. Br J Pharmacol. 1984 Apr;81(4):631–635. doi: 10.1111/j.1476-5381.1984.tb16128.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scheel-Krüger J. Behavioural and biochemical comparison of amphetamine derivatives, cocaine, benztropine and tricyclic anti-depressant drugs. Eur J Pharmacol. 1972 Apr;18(1):63–73. doi: 10.1016/0014-2999(72)90132-x. [DOI] [PubMed] [Google Scholar]
  26. Snyder S. H. Amphetamine psychosis: a "model" schizophrenia mediated by catecholamines. Am J Psychiatry. 1973 Jan;130(1):61–67. doi: 10.1176/ajp.130.1.61. [DOI] [PubMed] [Google Scholar]
  27. Suppes T., Pinnock R. D. Sensitivity of neuronal dopamine response in the substantia nigra and ventral tegmentum to clozapine, metoclopramide and SCH 23390. Neuropharmacology. 1987 Apr;26(4):331–337. doi: 10.1016/0028-3908(87)90185-7. [DOI] [PubMed] [Google Scholar]

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