Skip to main content
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1993 Dec;56(12):1295–1302. doi: 10.1136/jnnp.56.12.1295

Investigation of the opioid system in absence seizures with positron emission tomography.

P A Bartenstein 1, J S Duncan 1, M C Prevett 1, V J Cunningham 1, D R Fish 1, A K Jones 1, S K Luthra 1, G V Sawle 1, D J Brooks 1
PMCID: PMC1015377  PMID: 8270930

Abstract

The neuroanatomical and pathophysiological basis of primary generalised absences is uncertain. Administration of endogenous opioids has been shown to result in absence-like seizures in animal models. Positron emission tomography scans were performed in eight patients with primary generalised epilepsy and eight control subjects. Regional cerebral blood flow was measured interictally with C15O2, after which a 90 minute dynamic study with the opioid-receptor ligand 11C-diprenorphine was performed. Serial absences were precipitated by hyperventilation for 10 minutes, starting 30-40 minutes after injection of diprenorphine. Absences, with generalised spike-wave discharges on the EEG, occurred for between 10% and 51% of the provocation period. No individual (normal or patient) had any interictal focal abnormalities of cerebral blood flow. After provocation of serial absence seizures, there was increased diprenorphine elimination from the association cortex, but not from the thalamus, basal ganglia, or cerebellum, compared with control subjects and patients scanned without provocation of absences. It was possible to simulate the observed increased diprenorphine elimination following seizures in cerebral cortex using a two tissue compartment model, with an estimated 15-41% decrease in the specific tracer uptake rate constant (k3). These results suggest that endogenous opioids are released in the association cortex at the time of serial absences, lead to increased receptor occupancy, and may have an important role in the pathophysiology of generalised absences.

Full text

PDF
1295

Images in this article

Selected References

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

  1. Bajorek J. G., Lee R. J., Lomax P. Neuropeptides: anticonvulsant and convulsant mechanisms in epileptic model systems and in humans. Adv Neurol. 1986;44:489–500. [PubMed] [Google Scholar]
  2. Coulter D. A., Huguenard J. R., Prince D. A. Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: calcium current reduction. Br J Pharmacol. 1990 Aug;100(4):800–806. doi: 10.1111/j.1476-5381.1990.tb14095.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Frey H. H., Voits M. Effect of psychotropic agents on a model of absence epilepsy in rats. Neuropharmacology. 1991 Jun;30(6):651–656. doi: 10.1016/0028-3908(91)90086-q. [DOI] [PubMed] [Google Scholar]
  4. Friston K. J., Passingham R. E., Nutt J. G., Heather J. D., Sawle G. V., Frackowiak R. S. Localisation in PET images: direct fitting of the intercommissural (AC-PC) line. J Cereb Blood Flow Metab. 1989 Oct;9(5):690–695. doi: 10.1038/jcbfm.1989.97. [DOI] [PubMed] [Google Scholar]
  5. Gloor P. Generalized epilepsy with spike-and-wave discharge: a reinterpretation of its electrographic and clinical manifestations. The 1977 William G. Lennox Lecture, American Epilepsy Society. Epilepsia. 1979 Oct;20(5):571–588. doi: 10.1111/j.1528-1157.1979.tb04840.x. [DOI] [PubMed] [Google Scholar]
  6. Green A. R., Peralta E., Hong J. S., Mao C. C., Atterwill C. K., Costa E. Alterations in GABA metabolism and Met-enkephalin content in rat brain following repeated electroconvulsive shocks. J Neurochem. 1978 Sep;31(3):607–611. doi: 10.1111/j.1471-4159.1978.tb07831.x. [DOI] [PubMed] [Google Scholar]
  7. Haffmans J., Dzoljic M. R. Effects of delta opioid antagonists on enkephalin-induced seizures. Pharmacology. 1987;34(2-3):61–65. doi: 10.1159/000138253. [DOI] [PubMed] [Google Scholar]
  8. Hong J. S., Wood P. L., Gillin J. C., Yang H. Y., Costa E. Changes of hippocampal Met-enkephalin content after recurrent motor seizures. Nature. 1980 May 22;285(5762):231–232. doi: 10.1038/285231a0. [DOI] [PubMed] [Google Scholar]
  9. Jackson H. C., Nutt D. J. Differential effects of selective mu-, kappa- and delta-opioid antagonists on electroshock seizure threshold in mice. Psychopharmacology (Berl) 1991;103(3):380–383. doi: 10.1007/BF02244293. [DOI] [PubMed] [Google Scholar]
  10. Jones A. K., Luthra S. K., Maziere B., Pike V. W., Loc'h C., Crouzel C., Syrota A., Jones T. Regional cerebral opioid receptor studies with [11C]diprenorphine in normal volunteers. J Neurosci Methods. 1988 Mar;23(2):121–129. doi: 10.1016/0165-0270(88)90184-7. [DOI] [PubMed] [Google Scholar]
  11. Lee R. J., McCabe R. T., Wamsley J. K., Olsen R. W., Lomax P. Opioid receptor alterations in a genetic model of generalized epilepsy. Brain Res. 1986 Aug 13;380(1):76–82. doi: 10.1016/0006-8993(86)91431-9. [DOI] [PubMed] [Google Scholar]
  12. Martin W. R., Powers W. J., Raichle M. E. Cerebral blood volume measured with inhaled C15O and positron emission tomography. J Cereb Blood Flow Metab. 1987 Aug;7(4):421–426. doi: 10.1038/jcbfm.1987.85. [DOI] [PubMed] [Google Scholar]
  13. Mayberg H. S., Sadzot B., Meltzer C. C., Fisher R. S., Lesser R. P., Dannals R. F., Lever J. R., Wilson A. A., Ravert H. T., Wagner H. N., Jr Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography. Ann Neurol. 1991 Jul;30(1):3–11. doi: 10.1002/ana.410300103. [DOI] [PubMed] [Google Scholar]
  14. Neumaier J. F., Chavkin C. Release of endogenous opioid peptides displaces [3H]diprenorphine binding in rat hippocampal slices. Brain Res. 1989 Jul 31;493(2):292–302. doi: 10.1016/0006-8993(89)91164-5. [DOI] [PubMed] [Google Scholar]
  15. Patel V. K., Abbott L. C., Rattan A. K., Tejwani G. A. Increased methionine-enkephalin levels in genetically epileptic (tg/tg) mice. Brain Res Bull. 1991 Dec;27(6):849–852. doi: 10.1016/0361-9230(91)90221-5. [DOI] [PubMed] [Google Scholar]
  16. Ramabadran K., Bansinath M. Endogenous opioid peptides and epilepsy. Int J Clin Pharmacol Ther Toxicol. 1990 Feb;28(2):47–62. [PubMed] [Google Scholar]
  17. Richards M. L., Sadée W. In vivo opiate receptor binding of oripavines to mu, delta and kappa sites in rat brain as determined by an ex vivo labeling method. Eur J Pharmacol. 1985 Aug 27;114(3):343–353. doi: 10.1016/0014-2999(85)90379-6. [DOI] [PubMed] [Google Scholar]
  18. Sadzot B., Price J. C., Mayberg H. S., Douglass K. H., Dannals R. F., Lever J. R., Ravert H. T., Wilson A. A., Wagner H. N., Jr, Feldman M. A. Quantification of human opiate receptor concentration and affinity using high and low specific activity [11C]diprenorphine and positron emission tomography. J Cereb Blood Flow Metab. 1991 Mar;11(2):204–219. doi: 10.1038/jcbfm.1991.52. [DOI] [PubMed] [Google Scholar]
  19. Simantov R., Lotem J., Levy R. Selectivity in the control of opiate receptor density in the animal and in cultured fetal brain cells. Neuropeptides. 1984 Dec;5(1-3):197–200. doi: 10.1016/0143-4179(84)90061-1. [DOI] [PubMed] [Google Scholar]
  20. Snead O. C., 3rd, Bearden L. J. Anticonvulsants specific for petit mal antagonize epileptogenic effect of leucine enkephalin. Science. 1980 Nov 28;210(4473):1031–1033. doi: 10.1126/science.6254150. [DOI] [PubMed] [Google Scholar]
  21. Theodore W. H., Brooks R., Margolin R., Patronas N., Sato S., Porter R. J., Mansi L., Bairamian D., DiChiro G. Positron emission tomography in generalized seizures. Neurology. 1985 May;35(5):684–690. doi: 10.1212/wnl.35.5.684. [DOI] [PubMed] [Google Scholar]
  22. Tortella F. C., Cowan A. Studies on opioid peptides as endogenous anticonvulsants. Life Sci. 1982 Nov 15;31(20-21):2225–2228. doi: 10.1016/0024-3205(82)90124-2. [DOI] [PubMed] [Google Scholar]
  23. Tortella F. C. Endogenous opioid peptides and epilepsy: quieting the seizing brain? Trends Pharmacol Sci. 1988 Oct;9(10):366–372. doi: 10.1016/0165-6147(88)90256-8. [DOI] [PubMed] [Google Scholar]
  24. Tortella F. C., Long J. B. Endogenous anticonvulsant substance in rat cerebrospinal fluid after a generalized seizure. Science. 1985 May 31;228(4703):1106–1108. doi: 10.1126/science.2986292. [DOI] [PubMed] [Google Scholar]
  25. Vindrola O., Briones R., Asai M., Fernández-Guardiola A. Amygdaloid kindling enhances the enkephalin content in the rat brain. Neurosci Lett. 1981 Jan 1;21(1):39–43. doi: 10.1016/0304-3940(81)90054-9. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES