Abstract
Seizures induced by three convulsant treatment produced differential effects on the concentration of acetylcholine in rat brain. Status epilepticus induced by (i) coadministration of lithium and pilocarpine caused massive increases in the concentration of acetylcholine in the cerebral cortex and hippocampus, (ii) a high dose of pilocarpine did not cause an increase of acetylcholine, and (iii) kainate increased acetylcholine, but the magnitude was lower than with the lithium/pilocarpine model. The finding that the acetylcholine concentration increases in two models of status epilepticus in the cortex and hippocampus is in direct contrast with manyin vitro reports in which excessive stimulation causes depletion of acetylcholine. The concentration of choline increased during seizures with all three models. This is likely to be due to calcium- and agonist-induced activation of phospholipase C and/or D activity causing cleavage of choline-containing lipids. The excessive acetylcholine present during status epilepticus induced by lithium and pilocarpine was responsive to pharmacological manipulation. Atropine tended to decrease acetylcholine, similar to its effects in controls. The N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, reduced the excessive concentration of acetylcholine, especially in the cortex. Inhibition of choline uptake by hemicholinium-3 (HC-3) administered icv reduced the acetylcholine concentration in controls and when given to rats during status epilepticus. These results demonstrate that the rat brain concentrations of acetylcholine and choline can increase during status epilepticus. The accumulated acetylcholine was not in a static, inactive compartment, but was actively turning-over and was responsive to drug treatments. Excessive concentrations of acetylcholine and/or choline may play a role in seizure maintenance and in the neuronal damage and lethality associated with status epilepticus.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Jope, R. S., Simonato, M., and Lally, K. 1987. Acetylcholine content in rat brain is elevated by status epilepticus induced by lithium and pilocarpine. J. Neurochem. 49:944–951.
Honchar, M. P., Olney, J. W., and Sherman, W. R. 1983. Systemic cholinergic agents induce seizures and brain damage in lithium-treated rats. Science 220:323–325.
Jope, R. S., Morrisett, R. A., and Snead, O. C. 1986. Characterization of lithium potentiation of pilocarpine-induced status epilepticus in rats. Exp. Neurol. 91:471–480.
Morrisett, R. A., Jope, R. S., and Snead, O. C. 1987. Status epilepticus is produced by administration of cholinergic agonists to lithium-treated rats: Comparison with kainic acid. Exp. Neurol. 98:594–605.
Ormandy, G. C., Jope, R. S., and Snead, O. C. 1989. Anticonvulsant actions of MK-801 on the lithium-pilocarpine model of status epilepticus in rats. Exp. Neurol. 106:172–180.
Jenden, D. J. 1980. Regulation of acetylcholine synthesis and release. Pages 3–15,in H. I. Yamamura, R. W. Olsen and E. Usdin (eds.)Pharmacology and Biochemistry of Neurotransmitter Receptors, Elsevier, Amsterdam.
Ben-Ari, Y. 1985. Limbic seizure and brain damage produced by kainic acid: Mechanisms and relevance to human temporal lobe epilepsy. Neurosci. 14:375–403.
Jope, R. S., and Johnson, G. V. W. 1986. Quinacrine and 2-(4-phenylpiperidino)cyclohexanol (AH5183) inhibit acetylcholine release and synthesis in rat brain slices. Molec. Pharmacol. 29:45–51.
Jenden, D. J., Roch, M., and Booth, R. A. 1973. Simultaneous measurement of endogenous and deuterium labelled tracer variants of choline and acetylcholine in subpicomole quatities by gas chromatography mass spectrometry. Anal. Biochem. 55:438–448.
Turski, W. A., Cavalheiro, E. A., Schwarz, M., Czuczwar, S. J., Kleinrok, A., and Turski, L. 1983. Limbic seizures produced by pilocarpine in rats: Behavioral, electroencephalographic and neuropathological study. Behav. Brain Res. 9:315–336.
Ormandy, G. C., Song, L., and Jope, R. S. 1991. Analysis of the convulsant-potentiating effects of lithium in rats. Exp. Neurol. 111:356–361.
Scatton, B., and Lehmann, J. 1982. N-methyl-D-aspartate type receptors mediate striatal3H-acetylcholine release evoked by excitatory amino acids. Nature 297:422–424.
Löffelholz, K. 1989. Receptor regulation of choline phospholipid hydrolysis. Biochem. Pharmacol. 38:1543–1549.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jope, R.S., Gu, X. Seizures increase acetylcholine and choline concentrations in rat brain regions. Neurochem Res 16, 1219–1226 (1991). https://doi.org/10.1007/BF00966699
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00966699