Neurochemical Research

, Volume 17, Issue 8, pp 779–783

Effects of morphine andd-Ala2-d-Leu5-enkephalin in the seizure-susceptible El mouse

  • Seiji Koide
  • Hiroshi Onishi
  • Sakae Yamagami
  • Yukio Kawakita
Original Articles

Abstract

Opioid agonists were used to investigate the modulation of seizures in the seizure-susceptible El mouse. Morphine andd-Ala2-d-Leu5-enkephalin (DADLE) were injected subcutaneously or intracisternally as prototypic agonists for μ and δ opioid receptors. Systemic or intracisternal injection of both morphine and DADLE decreased the incidence of seizures and the seizure score in El mice in a dose-dependent manner. The anticonvulsant effects of morphine and DADLE were reversed by naloxone (2 mg/kg, s.c.). This implies that opioid agonists have anticonvulsant properties which are mediated by μ and δ opioid receptors. In conclusion, a deficit in endogenous opioid peptides, which act as anticonvulsants may play a significant role in the etiology or pathophysiology of seizures in the El mouse.

Key Words

El mouse morphine enkephalins seizure epilepsy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Frederickson, R. C. A., and Chipkin, R. E. 1988. Endogenous opioids and pain: Status of human studies and new treatment concepts. Prog. Brain Res. 77:407–417.Google Scholar
  2. 2.
    Grossman, A. 1985. Opioids and stress in man. J. Endocrinol. 119:377–381.Google Scholar
  3. 3.
    Reid, L. D. 1985. Endogenous opioid peptides and regulation of drinking and feeding. Am. J. Clin. Nutr. 42:1099–1132.Google Scholar
  4. 4.
    Urca, G., Frenk, H., Liebeskind, J. C., and Taylor, A. N. 1977. Morphine and enkephalin: Analgesic and epileptic properties. Science 197:83–86.Google Scholar
  5. 5.
    Henriksen, S. J., Bloom, F. E., Ling, N., and Guillemin, R. 1977. Induction of limbic scizures by endorphins and opiate alkaloids: Electrophysiological and behavioral correlates. Soc. Neurosci. Abstr. 3:293.Google Scholar
  6. 6.
    Tortella, F. C., Echevarria, E., Lipkowski, A. W., Takemori, A. E., Portoghese, P. S., and Holaday, J. W. 1989. Selective kappa antagonist properties of nor-binaltorphimine in the rat MES seizure model. Life Sci. 44:661–665.Google Scholar
  7. 7.
    Tortella, F. C., Robles, L., Echevarria, E., Hunter, J. C., and Hughes, J. 1990. PD117302, a selective nonpeptide opioid kappa agonist, protects against NMDA and maximal electroshock convulsions in rats. Life Sci. 46:PL1–7.Google Scholar
  8. 8.
    Tortella, F. C., Cowan, A., and Adler, M. W. 1981. Comparison of the anticonvulsant effects of opioid peptides and etorphine in rats after ICV administration. Life Sci. 10:1039–1045.Google Scholar
  9. 9.
    Tortella, F. C. 1988. Endogenous opioid peptides and epilepsy: quieting the seizing brain? Trends Pharmacol. Sci. 9:366–372.Google Scholar
  10. 10.
    Frenk, H. 1983. Pro-and anticonvulsant actions of morphine and the endogenous opioids: Involvement and interactions of multiple opiate and non-opiate systems. Brain Res. Rev. 6:197–210.Google Scholar
  11. 11.
    Albertson, T. E., Joy, R. M., and Stark, L. G. 1984. Modification of kindled amygdaloid seizures by opiate agonists and antagonists. J. Pharmacol. Exp. Ther. 228:620–627.Google Scholar
  12. 12.
    McNamara, J. O., Bonhaus, D. W., Shin, C., Crain, B. J., Gellman, R. L., and Giaccino, J. L. 1985. The kindling model of epilepsy: A critical review CRC Crit. Rev. Clin. Neurobiol. 1:341–391.Google Scholar
  13. 13.
    Stone, W. S., Eggleton, C. E., and Berman, R. F. 1982. Opiate modification of amygdaloid-kindled seizures in rats. Pharmacol. Biochem. Behav. 16:751–756.Google Scholar
  14. 14.
    Chen, C. S., Gates, G. R., and Reynoldson, J. A. 1976. Effect of morphine and naloxone on priming-induced audiogenic seizures in BALB/c mice. Br. J. Pharmacol. 58:517–520.Google Scholar
  15. 15.
    Meldrum, B. S., Menini, Ch., Stutzmann, J. M., and Naquet, R. 1979. Effects of opiate-like peptides, morphine, and naloxone in the photosensitive baboon, papio papio. Brain Res. 170:333–348.Google Scholar
  16. 16.
    Bajorek, J. G., and Lomax, P. 1982. Modulation of spontaneous seizures in the Mongolian gerbil: Effects of β-endorphin. Peptides 3:83–86.Google Scholar
  17. 17.
    Lee, R. J., Bajorek, J. G., and Lomax, P. 1983. Opioid peptides and seizures in the spontaneously epileptic Mongolian gerbil. Life Sci. 33:567–570.Google Scholar
  18. 18.
    Lee, R. J., Bajorek, J. G., and Lomax, P. 1984. Similar anticonvulsant, but unique behavioural effects of opioid agonists in the seizure-sensitive Mongolian gerbil. Neurophamacology. 23:517–524.Google Scholar
  19. 19.
    Seyfried, T. N., and Glaser, G. H. 1985. A review of mouse mutants as genetic models of epilepsy. Epilepsia 26:143–150.Google Scholar
  20. 20.
    Mori, A. 1988. El mice: Neurochemical approach to the seizure mechanism. Neurosciences 14:275–285.Google Scholar
  21. 21.
    Suzuki, J. 1976. Paroxysmal discharges in the electroencephalogram of the El mouse. Experimentia 32:336–338.Google Scholar
  22. 22.
    Onishi, H., Soma, T., Yamagami, S., and Kawakita, Y. 1989. Alteration of opioid receptors in seizure-susceptible El mouse brain. Neurochem. Res. 14:31–35.Google Scholar
  23. 23.
    Onishi, H., Koide, S., Yamagami, S., and Kawakita, Y. 1990. Developmental and regional alteration of methionine enkephalin-like immunoreactivity in seizure-susceptible El mouse brain. Neurochem. Res. 15:83–87.Google Scholar
  24. 24.
    Ueda, H., Amano, H., Shiomi, H., and Takagi, H. 1979. Comparison of the analgesic effects of various opioid peptides by a newly devised intracisternal injection technique in conscious mice. Eur. J. Pharmacol. 56:265–268.Google Scholar
  25. 25.
    Dingledine, R., Iversen, L. L., and Breuker, E. 1978. Naloxone as a GABA antagonist: Evidence from iontophoretic receptor binding and convulsant studies. Eur. J. Pharmacol. 47:19–27.Google Scholar
  26. 26.
    Werz, M. A., and MacDonald, R. L. 1982. Opiate alkaloids antagonize postysynaptic glycine and GABA responses: Correlation with convulsant action. Brain Res. 236:107–119.Google Scholar
  27. 27.
    Banks, W. A., and Kastin, A. J. 1987. Saturable transport of peptides across the blood-brain barrier. Life Sci. 41:1319–1338.Google Scholar
  28. 28.
    Banks, W. A., and Kastin, A. J. 1990. Peptide transport systems for opiates across the blood-brain barrier. Am. J. Physiol. 259:E1–10.Google Scholar

Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • Seiji Koide
    • 1
  • Hiroshi Onishi
    • 1
  • Sakae Yamagami
    • 1
  • Yukio Kawakita
    • 1
  1. 1.Department of NeuropsychiatryOsaka City University Medical SchoolOsakaJapan

Personalised recommendations