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. 1990 Nov;101(3):599–604. doi: 10.1111/j.1476-5381.1990.tb14127.x

Acetylcholinesterase activity in regions of mouse brain following acute and chronic treatment with a benzodiazepine inverse agonist.

M E Appleyard 1, S C Taylor 1, H J Little 1
PMCID: PMC1917736  PMID: 1963800

Abstract

1. Chronic administration of the benzodiazepine inverse agonist FG 7142 has previously been shown to induce seizure activity in mice. In the present study we have investigated the effects of acute and chronic treatment with FG 7142 in mice on the levels of acetylcholinesterase activity in cortex, hippocampus, midbrain and striatum. We have also investigated the effects of acute and chronic stress in the form of handling (vehicle-injection) on acetylcholinesterase levels. 2. A single dose of FG 7142 produced a marked elevation of total acetylcholinesterase activities in the hippocampus and midbrain when compared with vehicle-injected control levels, but the levels were not different from those in unhandled animals. 3. Acute stress, in the form of vehicle-injection produced decreases in cortical and hippocampal soluble acetylcholinesterase activity but FG 7142 had no effect upon these stress-induced changes. 4. Total cortical and hippocampal acetylcholinesterase activities were increased by 56% and 16% respectively in the chronic FG 7142-treated mice that exhibited seizure activity (compared with vehicle-injected controls). 5. Soluble acetylcholinesterase activity in the midbrain was decreased to 82% of control levels only in animals that had undergone FG 7142-induced kindling. Smaller or no changes in acetylcholinesterase activity in the midbrain were observed in chronically FG 7142-treated animals that exhibited no seizure activity. 6. Mice that did not demonstrate seizure activity in response to chronic FG 7142 treatment showed alterations in the soluble acetylcholinesterase activities of the hippocampus and midbrain.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Appleyard M. E., Green A. R., Greenfield S. A. Acetylcholinesterase activity rises in rat cerebrospinal fluid post-ictally; effect of a substantia nigra lesion on this rise and on seizure threshold. Br J Pharmacol. 1987 May;91(1):149–154. doi: 10.1111/j.1476-5381.1987.tb08993.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Appleyard M. E., Green A. R., Smith A. D. Acetylcholinesterase activity in regions of the rat brain following a convulsion. J Neurochem. 1986 Jun;46(6):1789–1793. doi: 10.1111/j.1471-4159.1986.tb08497.x. [DOI] [PubMed] [Google Scholar]
  3. Arnold P. S., Racine R. J., Wise R. A. Effects of atropine, reserpine, 6-hydroxydopamine, and handling on seizure development in the rat. Exp Neurol. 1973 Aug;40(2):457–470. doi: 10.1016/0014-4886(73)90087-3. [DOI] [PubMed] [Google Scholar]
  4. BUKIN Y. W. Partial recovery of glutamic-oxaloacetic transaminase activity in the infarcted areas of the myocardium in rabbits during stimulation of protein synthesis. Nature. 1963 May 18;198:692–693. doi: 10.1038/198692b0. [DOI] [PubMed] [Google Scholar]
  5. Babington R. G., Wedeking P. W. The pharmacology of seizures induced by sensitization with low intensity brain stimulation. Pharmacol Biochem Behav. 1973 Jul-Aug;1(4):461–467. doi: 10.1016/0091-3057(73)90013-0. [DOI] [PubMed] [Google Scholar]
  6. Chu N. S., Rutledge L. T., Sellinger O. Z. The effect of cortical undercutting and long-term electrical stimulation on synaptic acetylcholinesterase. Brain Res. 1971 Jun 18;29(2):323–330. doi: 10.1016/0006-8993(71)90036-9. [DOI] [PubMed] [Google Scholar]
  7. Chubb I. W., Smith A. D. Isoenzymes of soluble and membrane-bound acetylcholinesterase in boine splanchnic nerve and adrenal medulla. Proc R Soc Lond B Biol Sci. 1975 Nov 18;191(1103):245–261. doi: 10.1098/rspb.1975.0126. [DOI] [PubMed] [Google Scholar]
  8. Coscina D. V., Goodman J., Godse D. D., Stancer H. C. Taming effects of handling on 6-hydroxydopamine induced ratge. Pharmacol Biochem Behav. 1975 May-Jun;3(3):525–528. doi: 10.1016/0091-3057(75)90067-2. [DOI] [PubMed] [Google Scholar]
  9. ECHLIN F. A., BATTISTA A. EPILEPTIFORM SEIZURES FROM CHRONIC ISOLATED CORTEX. Arch Neurol. 1963 Aug;9:154–170. doi: 10.1001/archneur.1963.00460080064009. [DOI] [PubMed] [Google Scholar]
  10. Garant D. S., Gale K. Lesions of substantia nigra protect against experimentally induced seizures. Brain Res. 1983 Aug 22;273(1):156–161. doi: 10.1016/0006-8993(83)91105-8. [DOI] [PubMed] [Google Scholar]
  11. Graham-Jones S., Fillenz M., Gray J. A. The effects of footshock and handling on tyrosine hydroxylase activity in synaptosomes and solubilised preparations from rat brain. Neuroscience. 1983 Jul;9(3):679–686. doi: 10.1016/0306-4522(83)90184-7. [DOI] [PubMed] [Google Scholar]
  12. Greenfield S. A., Jack J. J., Last A. T., French M. An electrophysiological action of acetylcholinesterase independent of its catalytic site. Exp Brain Res. 1988;70(2):441–444. doi: 10.1007/BF00248370. [DOI] [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. Little H. J., Nutt D. J., Taylor S. C. Acute and chronic effects of the benzodiazepine receptor ligand FG 7142: proconvulsant properties and kindling. Br J Pharmacol. 1984 Dec;83(4):951–958. doi: 10.1111/j.1476-5381.1984.tb16536.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Little H. J., Nutt D. J., Taylor S. C. Selective changes in the in vivo effects of benzodiazepine receptor ligands after chemical kindling with FG 7142. Neuropharmacology. 1987 Jan;26(1):25–31. doi: 10.1016/0028-3908(87)90040-2. [DOI] [PubMed] [Google Scholar]
  16. Little H. J., Nutt D. J., Taylor S. C. The effects of drugs acting at the GABAA-receptor/ionophore after chemical kindling with the benzodiazepine receptor ligand FG 7142. Br J Pharmacol. 1986 Jul;88(3):507–514. doi: 10.1111/j.1476-5381.1986.tb10230.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McNamara J. O., Rigsbee L. C., Galloway M. T. Evidence that Substantia Nigra is crucial to neural network of kindled seizures. Eur J Pharmacol. 1983 Jan 21;86(3-4):485–486. doi: 10.1016/0014-2999(83)90202-9. [DOI] [PubMed] [Google Scholar]
  18. Morin A. M. Beta-carboline kindling of the benzodiazepine receptor. Brain Res. 1984 Oct 29;321(1):151–154. doi: 10.1016/0006-8993(84)90692-9. [DOI] [PubMed] [Google Scholar]
  19. Nutt D. J., Cowen P. J., Green A. R. Studies on the post-ictal rise in seizure threshold. Eur J Pharmacol. 1981 May 8;71(2-3):287–295. doi: 10.1016/0014-2999(81)90031-5. [DOI] [PubMed] [Google Scholar]
  20. Olney J. W., de Gubareff T., Labruyere J. Seizure-related brain damage induced by cholinergic agents. Nature. 1983 Feb 10;301(5900):520–522. doi: 10.1038/301520a0. [DOI] [PubMed] [Google Scholar]
  21. ROSENBERG P., ECHLIN F. A. CHOLINESTERASE ACTIVITY OF CHRONIC PARTIALLY ISOLATED CORTEX. Neurology. 1965 Aug;15:700–707. doi: 10.1212/wnl.15.8.700. [DOI] [PubMed] [Google Scholar]
  22. Robertson H. A., Riives M. L. A benzodiazepine antagonist is an anticonvulsant in an animal model for limbic epilepsy. Brain Res. 1983 Jul 4;270(2):380–382. doi: 10.1016/0006-8993(83)90619-4. [DOI] [PubMed] [Google Scholar]
  23. Singh H. C., Singh R. H., Udupa K. N. Electric shock induced changes in free, bound & total acetylcholine & acetylcholinesterase in different brain regions of rats. Indian J Exp Biol. 1979 Mar;17(3):304–306. [PubMed] [Google Scholar]
  24. Stanford C., Fillenz M., Ryan E. The effect of repeated mild stress on cerebral cortical adrenoceptors and noradrenaline synthesis in the rat. Neurosci Lett. 1984 Mar 23;45(2):163–167. doi: 10.1016/0304-3940(84)90093-4. [DOI] [PubMed] [Google Scholar]
  25. Stanford S. C., Little H. J., Nutt D. J., Taylor S. C. Effects of chronic treatment with benzodiazepine receptor ligands on cortical adrenoceptors. Eur J Pharmacol. 1986 Sep 23;129(1-2):181–184. doi: 10.1016/0014-2999(86)90351-1. [DOI] [PubMed] [Google Scholar]
  26. Turski W. A., Czuczwar S. J., Kleinrok Z., Turski L. Cholinomimetics produce seizures and brain damage in rats. Experientia. 1983 Dec 15;39(12):1408–1411. doi: 10.1007/BF01990130. [DOI] [PubMed] [Google Scholar]

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