Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1976 Mar;256(1):1–21. doi: 10.1113/jphysiol.1976.sp011308

Dopamine evoked inhibition of single cells of the feline putamen and basolateral amygdala.

Y Ben-Ari, J S Kelly
PMCID: PMC1309288  PMID: 933014

Abstract

1. In cats under pentobarbitone or halothane anaesthesia, neurones of the putamen and basolateral amygdala were inhibited with a similar time course by iontophoretic applications of dopamine and gamma-aminobutyric acid (GABA), ejected with relatively short (20 sec) low intensity (less than 40 nA) pulses of positive current from five and seven barrelled extracellular micropipettes. The use of a stereotaxically positioned guide tube, sealed to the skull with dental cement, made it possible to obtain stable recording conditions and to correlate the stereotaxic position of the cells with the position of the micro-electrode tracks determined histologically by the post-mortem reconstruction of serial sections. 2. Since in cats anaesthetized with pentobarbitone none of the cells were found to be spontaneously active, the relative potency of dopamine and GABA were compared on glutamate excited cells. Approximately 2-5 times more current was required to release sufficient dopamine to cause just submaximal inhibition, equal in magnitude and duration to that evoked by GABA. 3. In nitrous oxide/halothane anaesthetized cats, approximately one quarter of the cells were spontaneously active. Relative potency studies showed that for dopamine, currents 2-0 and 1-6 times larger than those used for GABA were required to inhibit glutamate excited and spontaneously active cells respectively. 4. When the depth distribution of the cells was compared with the sensitivity of the cells to dopamine and GABA, the most sensitive cells were found to lie within the putamen and the basolateral amygdala. 5. On more than one third of the cells tested, iontophoretic application of the neuroleptic, alpha-flupenthixol of more than 3 or 4 min in duration, greatly reduced or abolished the inhibition of the cells by dopamine without impairing their sensitivity to GABA. 6. In four cats, large I.V. injections of alpha-flupenthixol (10 mg/kg) and the more potent neuroleptic pimozide (1 mg/kg) had no significant effect on the dopamine or GABA sensitivity of seventy cells in the putamen and basolateral amygdala. 7. Our results are in keeping with the view that dopamine has a predominantly inhibitory action in the mammalian forebrain. However the failure of I.V. neuroleptics to modify the sensitivity of the cells to dopamine suggests that the dramatic effects of neuroleptics on animal behaviour may not be explicable simply in terms of a generalized blockade of dopamine receptors at post-synaptic sites.

Full text

PDF
1

Images in this article

20-2A
on p.20-2
20-2B
on p.20-2

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ben-Ari Y., Kelly J. S. Proceedings: Iontophoretic and intravenous effects of the neuroleptic, alpha-flupenthixol, on dopamine evoked inhibition. J Physiol. 1974 Oct;242(2):66P–67P. [PubMed] [Google Scholar]
  2. Ben-Ari Y., Le Gal le Salle G., Champagnat J. C. Lateral amygdala unit acitvity: I. Relationship between spontaneous and evoked activity. Electroencephalogr Clin Neurophysiol. 1974 Nov;37(5):449–461. doi: 10.1016/0013-4694(74)90086-8. [DOI] [PubMed] [Google Scholar]
  3. Ben-Ari Y. Plasticity at unitary level. I. An experimental design. Electroencephalogr Clin Neurophysiol. 1972 Jun;32(6):655–665. doi: 10.1016/0013-4694(72)90102-2. [DOI] [PubMed] [Google Scholar]
  4. Ben-Ari Y., Zigmond R. E., Moore K. E. Regional distribution of tyrosine hydroxylase, norepinephrine and dopamine within the amygdaloid complex of the rat. Brain Res. 1975 Apr 4;87(1):96–101. doi: 10.1016/0006-8993(75)90786-6. [DOI] [PubMed] [Google Scholar]
  5. Biscoe T. J., Straughan D. W. Micro-electrophoretic studies of neurones in the cat hippocampus. J Physiol. 1966 Mar;183(2):341–359. doi: 10.1113/jphysiol.1966.sp007869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bloom F. E., Costa E., Salmoiraghi G. C. Anesthesia and the responsiveness of individual neurons of the caudate nucleus of the cat to acetylcholine, norepinephrine and dopamine administered by microelectrophoresis. J Pharmacol Exp Ther. 1965 Nov;150(2):244–252. [PubMed] [Google Scholar]
  7. Bradley P. B., Candy J. M. Iontophoretic release of acetylcholine, noradrenaline, 5-hydroxytryptamine and D-lysergic acid diethylamide from micropipettes. Br J Pharmacol. 1970 Oct;40(2):194–201. doi: 10.1111/j.1476-5381.1970.tb09913.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bradley P. B., Dray A. Modification of the responses of brain stem neurones to transmitter substances by anaesthetic agents. Br J Pharmacol. 1973 Jun;48(2):212–224. doi: 10.1111/j.1476-5381.1973.tb06907.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bradshaw C. M., Roberts M. H., Szabadi E. Kinetics of the release of noradrenaline from micropipettes: interaction between ejecting and retaining currents. Br J Pharmacol. 1973 Dec;49(4):667–677. doi: 10.1111/j.1476-5381.1973.tb08543.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brownstein M., Saavedra J. M., Palkovits M. Norepinephrine and dopamine in the limbic system of the rat. Brain Res. 1974 Oct 25;79(3):431–436. doi: 10.1016/0006-8993(74)90440-5. [DOI] [PubMed] [Google Scholar]
  11. CARLSSON A. The occurrence, distribution and physiological role of catecholamines in the nervous system. Pharmacol Rev. 1959 Jun;11(2 Pt 2):490–493. [PubMed] [Google Scholar]
  12. Catchlove R. F., Krnjević K., Maretić H. Similarity between effects of general anesthetics and dinitrophenol on cortical neurones. Can J Physiol Pharmacol. 1972 Nov;50(11):1111–1114. doi: 10.1139/y72-162. [DOI] [PubMed] [Google Scholar]
  13. Connor J. D. Caudate nucleus neurones: correlation of the effects of substantia nigra stimulaton with iontophoretic dopamine. J Physiol. 1970 Jul;208(3):691–703. doi: 10.1113/jphysiol.1970.sp009143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Coyle J. T. Tyrosine hydroxylase in rat brain--cofactor requirements, regional and subcellular distribution. Biochem Pharmacol. 1972 Jul 15;21(14):1935–1944. doi: 10.1016/0006-2952(72)90006-8. [DOI] [PubMed] [Google Scholar]
  15. Curtis D. R., Johnston G. A. Amino acid transmitters in the mammalian central nervous system. Ergeb Physiol. 1974;69(0):97–188. doi: 10.1007/3-540-06498-2_3. [DOI] [PubMed] [Google Scholar]
  16. Dun N., Nishi S. Effects of dopamine on the superior cervical ganglion of the rabbit. J Physiol. 1974 May;239(1):155–164. doi: 10.1113/jphysiol.1974.sp010560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. FUXE K. EVIDENCE FOR THE EXISTENCE OF MONOAMINE NEURONS IN THE CENTRAL NERVOUS SYSTEM. IV. DISTRIBUTION OF MONOAMINE NERVE TERMINALS IN THE CENTRAL NERVOUS SYSTEM. Acta Physiol Scand Suppl. 1965:SUPPL 247–247:37+. [PubMed] [Google Scholar]
  18. Feltz P. Dopamine, amino acids and caudate unitary responses to nigral stimulation. J Physiol. 1969 Nov;205(2):8P–9P. [PubMed] [Google Scholar]
  19. Freedman R., Hoffer B. J. Phenothiazine antagonism of the noradrenergic inhibition of cerebellar Purkinje neurons. J Neurobiol. 1975 May;6(3):277–288. doi: 10.1002/neu.480060304. [DOI] [PubMed] [Google Scholar]
  20. Godfraind J. M. Localisation de l'extrémité de microélectrodes de verre dans le système nerveux central par électrophorèse de pontamine. J Physiol (Paris) 1969;61 (Suppl 2):436–437. [PubMed] [Google Scholar]
  21. Gonzalez-Vegas J. A. Antagonism of dopamine-mediated inhibition in the nigro-striatal pathway: a mode of action of some catatonia-inducing drugs. Brain Res. 1974 Nov 15;80(2):219–228. doi: 10.1016/0006-8993(74)90686-6. [DOI] [PubMed] [Google Scholar]
  22. Herz A., Zieglgänsberger W. The influence of microelectrophoretically applied biogenic amines, cholinomimetics and procaine on synaptic excitation in the corpus striatum. Int J Neuropharmacol. 1968 May;7(3):221–230. doi: 10.1016/0028-3908(68)90029-4. [DOI] [PubMed] [Google Scholar]
  23. Hoffer B. J., Neff N. H., Siggins G. R. Microiontophoretic release of norepinephrine from micropipettes. Neuropharmacology. 1971 Mar;10(21):175–180. doi: 10.1016/0028-3908(71)90038-4. [DOI] [PubMed] [Google Scholar]
  24. Hökfelt T., Ljungdahl A., Fuxe K., Johansson O. Dopamine nerve terminals in the rat limbic cortex: aspects of the dopamine hypothesis of schizophrenia. Science. 1974 Apr 12;184(4133):177–179. doi: 10.1126/science.184.4133.177. [DOI] [PubMed] [Google Scholar]
  25. KUNTZMAN R., SHORE P. A., BOGDANSKI D., BRODIE B. B. Microanalytical procedures for fluorometric assay of brain DOPA-5HTP decarboxylase, norepinephrine and serotonin, and a detailed mapping of decarboxylase activity in brain. J Neurochem. 1961 Feb;6:226–232. doi: 10.1111/j.1471-4159.1961.tb13469.x. [DOI] [PubMed] [Google Scholar]
  26. Lee B. B., Mandl G., Stean J. P. Micro-electrode tip position marking in nervous tissue: a new dye method. Electroencephalogr Clin Neurophysiol. 1969 Dec;27(6):610–613. doi: 10.1016/0013-4694(69)90075-3. [DOI] [PubMed] [Google Scholar]
  27. McGeer P. L., Grewaal D. S., McGeer E. G. Influence of noncholinergic drugs on rat striatal acetylcholine levels. Brain Res. 1974 Nov 15;80(2):211–217. doi: 10.1016/0006-8993(74)90685-4. [DOI] [PubMed] [Google Scholar]
  28. McLennan H., York D. H. The action of dopamine on neurones of the caudate nucleus. J Physiol. 1967 Apr;189(3):393–402. doi: 10.1113/jphysiol.1967.sp008175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nielsen I. M., Pedersen V., Nymark M., Franck K. F., Boeck V., Fjalland B., Christensen A. V. The comparative pharmacology of flupenthixol and some reference neuroleptics. Acta Pharmacol Toxicol (Copenh) 1973;33(5):353–362. doi: 10.1111/j.1600-0773.1973.tb01537.x. [DOI] [PubMed] [Google Scholar]
  30. Rommelspacher H., Goldberg A. M., Kuhar M. J. Action of hemicholinium-3 on cholinergic nerve terminals after alteration of neuronal impulse flow. Neuropharmacology. 1974 Nov;13(10-11):1015–1023. doi: 10.1016/0028-3908(74)90092-6. [DOI] [PubMed] [Google Scholar]
  31. Seeman P., Lee T. Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science. 1975 Jun 20;188(4194):1217–1219. doi: 10.1126/science.1145194. [DOI] [PubMed] [Google Scholar]
  32. Sethy V. H., Van Woert M. H. Regulation of striatal acetylcholine concentration by dopamine receptors. Nature. 1974 Oct 11;251(5475):529–530. doi: 10.1038/251529a0. [DOI] [PubMed] [Google Scholar]
  33. Soudijn W., Van Wijngaarden I. Localization of ( 3 H)pimozide in the rat brain in relation to its anti-amphetamine potency. J Pharm Pharmacol. 1972 Oct;24(10):773–780. doi: 10.1111/j.2042-7158.1972.tb08881.x. [DOI] [PubMed] [Google Scholar]
  34. Spehlmann R., Stahl S. M. Neuronal hyposensitivity to dopamine in the caudate nucleus depleted of biogenic amines by tegmental lesions. Exp Neurol. 1974 Mar;42(3):703–706. doi: 10.1016/0014-4886(74)90091-0. [DOI] [PubMed] [Google Scholar]
  35. Spehlmann R. The effects of acetylcholine and dopamine on the caudate nucleus depleted of biogenic amines. Brain. 1975 Jun;98(2):219–230. doi: 10.1093/brain/98.2.219. [DOI] [PubMed] [Google Scholar]
  36. Straughan D. W., Legge K. F. The pharmacology of amygdaloid neurones. J Pharm Pharmacol. 1965 Oct;17(10):675–677. doi: 10.1111/j.2042-7158.1965.tb07587.x. [DOI] [PubMed] [Google Scholar]
  37. Thierry A. M., Blanc G., Sobel A., Stinus L., Glowinski J. Dopaminergic terminals in the rat cortex. Science. 1973 Nov 2;182(4111):499–501. doi: 10.1126/science.182.4111.499. [DOI] [PubMed] [Google Scholar]
  38. Ungerstedt U. Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand Suppl. 1971;367:1–48. doi: 10.1111/j.1365-201x.1971.tb10998.x. [DOI] [PubMed] [Google Scholar]
  39. Yarbrough G. G. Supersensitivity of caudate neurones after repeated administration of haloperidol. Eur J Pharmacol. 1975 Apr;31(2):367–369. doi: 10.1016/0014-2999(75)90062-x. [DOI] [PubMed] [Google Scholar]
  40. York D. H. Dopamine receptor blockade--a central action of chlorpromazine on striatal neurones. Brain Res. 1972 Feb 11;37(1):91–99. doi: 10.1016/0006-8993(72)90348-4. [DOI] [PubMed] [Google Scholar]
  41. York D. H. Possible dopaminergic pathway from substantia nigra to putamen. Brain Res. 1970 Jun 3;20(2):233–249. doi: 10.1016/0006-8993(70)90291-x. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES