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. 1991 Jun;103(2):1313–1320. doi: 10.1111/j.1476-5381.1991.tb09786.x

A calcium channel antagonist stereoselectively decreases ethanol withdrawal hyperexcitability but not that due to bicuculline, in hippocampal slices.

M A Whittington 1, H J Little 1
PMCID: PMC1908364  PMID: 1832063

Abstract

1. Extracellular recordings were made from CA1 area of isolated hippocampal slices of the mouse after chronic ethanol administration in vivo, with orthodromic stimulation of the Schaffer collateral/commissural fibres. 2. The (+)-isomer of the calcium channel antagonist PN 200-110 (isradipine) significantly decreased all the recorded signs of hyperexcitability in the slices during ethanol withdrawal. These included increased paired pulse potentiation and decreases in the thresholds for elicitation of single and multiple population spikes. 3. The (-)-isomer of PN 200-100 did not affect ethanol withdrawal hyperexcitability in the slices. 4. Neither isomer of PN 200-110 affected the field potentials in slices from control animals. 5. The gamma-aminobutyric acid (GABA) antagonist, bicuculline, lowered thresholds for eliciting population spikes in hippocampal slices from untreated animals. The active, (+)-isomer of PN 200-110 did not affect this action of bicuculline in hippocampal slices from untreated animals. 6. The stereoisomerism of the action of PN 200-110 on ethanol withdrawal hyperexcitability in the hippocampal slice was therefore the same as that seen in blockade of calcium channels. The results suggested that ethanol withdrawal hyperexcitability recorded in the isolated hippocampal slice involved increased activity of voltage-sensitive calcium channels.

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Selected References

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

  1. Akaike N., Kostyuk P. G., Osipchuk Y. V. Dihydropyridine-sensitive low-threshold calcium channels in isolated rat hypothalamic neurones. J Physiol. 1989 May;412:181–195. doi: 10.1113/jphysiol.1989.sp017610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes C. A. Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol. 1979 Feb;93(1):74–104. doi: 10.1037/h0077579. [DOI] [PubMed] [Google Scholar]
  3. Bean B. P. Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6388–6392. doi: 10.1073/pnas.81.20.6388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dolin S. J., Hunter A. B., Halsey M. J., Little H. J. Anticonvulsant profile of the dihydropyridine calcium channel antagonists, nitrendipine and nimodipine. Eur J Pharmacol. 1988 Jul 26;152(1-2):19–27. doi: 10.1016/0014-2999(88)90831-x. [DOI] [PubMed] [Google Scholar]
  5. Dolin S. J., Little H. J. Are changes in neuronal calcium channels involved in ethanol tolerance? J Pharmacol Exp Ther. 1989 Sep;250(3):985–991. [PubMed] [Google Scholar]
  6. Dolin S. J., Patch T. L., Rabbani M., Siarey R. J., Bowhay A. R., Little H. J. Nitrendipine decreases benzodiazepine withdrawal seizures but not the development of benzodiazepine tolerance or withdrawal signs. Br J Pharmacol. 1990 Nov;101(3):691–697. doi: 10.1111/j.1476-5381.1990.tb14142.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dolin S., Little H., Hudspith M., Pagonis C., Littleton J. Increased dihydropyridine-sensitive calcium channels in rat brain may underlie ethanol physical dependence. Neuropharmacology. 1987 Feb-Mar;26(2-3):275–279. doi: 10.1016/0028-3908(87)90220-6. [DOI] [PubMed] [Google Scholar]
  8. Durand D., Carlen P. L. Decreased neuronal inhibition in vitro after long-term administration of ethanol. Science. 1984 Jun 22;224(4655):1359–1361. doi: 10.1126/science.6328654. [DOI] [PubMed] [Google Scholar]
  9. Goldstein D. B., Pal N. Alcohol dependence produced in mice by inhalation of ethanol: grading the withdrawal reaction. Science. 1971 Apr 16;172(3980):288–290. doi: 10.1126/science.172.3980.288. [DOI] [PubMed] [Google Scholar]
  10. Greenberg D. A., Carpenter C. L., Messing R. O. Depolarization-dependent binding of the calcium channel antagonist, (+)-[3H]PN200-110, to intact cultured PC12 cells. J Pharmacol Exp Ther. 1986 Sep;238(3):1021–1027. [PubMed] [Google Scholar]
  11. Grover L. M., Teyler T. J. Two components of long-term potentiation induced by different patterns of afferent activation. Nature. 1990 Oct 4;347(6292):477–479. doi: 10.1038/347477a0. [DOI] [PubMed] [Google Scholar]
  12. Harris R. A., Hood W. F. Inhibition of synaptosomal calcium uptake by ethanol. J Pharmacol Exp Ther. 1980 Jun;213(3):562–568. [PubMed] [Google Scholar]
  13. Hirning L. D., Fox A. P., McCleskey E. W., Olivera B. M., Thayer S. A., Miller R. J., Tsien R. W. Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons. Science. 1988 Jan 1;239(4835):57–61. doi: 10.1126/science.2447647. [DOI] [PubMed] [Google Scholar]
  14. Hof R. P., Hof A., Ruegg U. T., Cook N. S., Vogel A. Stereoselectivity at the calcium channel: different profiles of hemodynamic activity of the enantiomers of the dihydropyridine derivative PN 200-110. J Cardiovasc Pharmacol. 1986 Mar-Apr;8(2):221–226. doi: 10.1097/00005344-198603000-00001. [DOI] [PubMed] [Google Scholar]
  15. Hof R. P., Hof A., Scholtysik G., Menninger K. Effects of the new calcium antagonist PN 200-110 on the myocardium and the regional peripheral circulation in anesthetized cats and dogs. J Cardiovasc Pharmacol. 1984 May-Jun;6(3):407–416. doi: 10.1097/00005344-198405000-00006. [DOI] [PubMed] [Google Scholar]
  16. Kendall D. A., Nahorski S. R. Dihydropyridine calcium channel activators and antagonists influence depolarization-evoked inositol phospholipid hydrolysis in brain. Eur J Pharmacol. 1985 Sep 10;115(1):31–36. doi: 10.1016/0014-2999(85)90580-1. [DOI] [PubMed] [Google Scholar]
  17. Lee W. L., Anwyl R., Rowan M. 4-Aminopyridine-mediated increase in long-term potentiation in CA1 of the rat hippocampus. Neurosci Lett. 1986 Sep 25;70(1):106–109. doi: 10.1016/0304-3940(86)90446-5. [DOI] [PubMed] [Google Scholar]
  18. Little H. J., Dolin S. J., Halsey M. J. Calcium channel antagonists decrease the ethanol withdrawal syndrome. Life Sci. 1986 Dec 1;39(22):2059–2065. doi: 10.1016/0024-3205(86)90356-5. [DOI] [PubMed] [Google Scholar]
  19. Littleton J. M., Little H. J., Whittington M. A. Effects of dihydropyridine calcium channel antagonists in ethanol withdrawal; doses required, stereospecificity and actions of Bay K 8644. Psychopharmacology (Berl) 1990;100(3):387–392. doi: 10.1007/BF02244612. [DOI] [PubMed] [Google Scholar]
  20. Llinás R. R. The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science. 1988 Dec 23;242(4886):1654–1664. doi: 10.1126/science.3059497. [DOI] [PubMed] [Google Scholar]
  21. Lovinger D. M., White G., Weight F. F. Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science. 1989 Mar 31;243(4899):1721–1724. doi: 10.1126/science.2467382. [DOI] [PubMed] [Google Scholar]
  22. Nowycky M. C., Fox A. P., Tsien R. W. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature. 1985 Aug 1;316(6027):440–443. doi: 10.1038/316440a0. [DOI] [PubMed] [Google Scholar]
  23. Reynolds J. N., Wu P. H., Khanna J. M., Carlen P. L. Ethanol tolerance in hippocampal neurons: adaptive changes in cellular responses to ethanol measured in vitro. J Pharmacol Exp Ther. 1990 Jan;252(1):265–271. [PubMed] [Google Scholar]
  24. Sanna E., Head G. A., Hanbauer I. Evidence for a selective localization of voltage-sensitive Ca2+ channels in nerve cell bodies of corpus striatum. J Neurochem. 1986 Nov;47(5):1552–1557. doi: 10.1111/j.1471-4159.1986.tb00794.x. [DOI] [PubMed] [Google Scholar]
  25. Takahashi K., Wakamori M., Akaike N. Hippocampal CA1 pyramidal cells of rats have four voltage-dependent calcium conductances. Neurosci Lett. 1989 Sep 25;104(1-2):229–234. doi: 10.1016/0304-3940(89)90359-5. [DOI] [PubMed] [Google Scholar]
  26. Thayer S. A., Murphy S. N., Miller R. J. Widespread distribution of dihydropyridine-sensitive calcium channels in the central nervous system. Mol Pharmacol. 1986 Dec;30(6):505–509. [PubMed] [Google Scholar]
  27. Ticku M. K., Lowrimore P., Lehoullier P. Ethanol enhances GABA-induced 36Cl-influx in primary spinal cord cultured neurons. Brain Res Bull. 1986 Jul;17(1):123–126. doi: 10.1016/0361-9230(86)90168-1. [DOI] [PubMed] [Google Scholar]
  28. Westenbroek R. E., Ahlijanian M. K., Catterall W. A. Clustering of L-type Ca2+ channels at the base of major dendrites in hippocampal pyramidal neurons. Nature. 1990 Sep 20;347(6290):281–284. doi: 10.1038/347281a0. [DOI] [PubMed] [Google Scholar]
  29. Whittington M. A., Little H. J. Patterns of changes in field potentials in the isolated hippocampal slice on withdrawal from chronic ethanol treatment of mice in vivo. Brain Res. 1990 Jul 23;523(2):237–244. doi: 10.1016/0006-8993(90)91492-y. [DOI] [PubMed] [Google Scholar]
  30. Wu P. H., Pham T., Naranjo C. A. Nifedipine delays the acquisition of tolerance to ethanol. Eur J Pharmacol. 1987 Jul 9;139(2):233–236. doi: 10.1016/0014-2999(87)90256-1. [DOI] [PubMed] [Google Scholar]

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