Advertisement

Psychopharmacology

, Volume 69, Issue 2, pp 163–171 | Cite as

Importance of the Locus coeruleus and involvement of α-adrenergic receptors in the post-decapitation reflex in the rat

  • Bruce A. Pappas
  • George R. Breese
  • Richard B. Mailman
  • Robert A. Mueller
Original Investigations

Abstract

The latency, duration, hindlimb kick frequency, and total activity components of the post-decapitation reflex (PDR) were measured in the rat using a movement-sensitive transducer. Reduction of brain and spinal cord norepinephrine (NE) caused by neonatal administration of 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine, which also reduced brain serotonin, decreased all components of the PDR. Depletion of serotonin or dopamine alone reduced the vigor of the reflex, suggesting that these pathways can influence the PDR but are not essential for the response. Lesions of neurons in the Locus coeruleus, made electrolytically or with 6-OHDA, decreased the intensity of the PDR, with the 6-OHDA-induced lesion being more effective. Depletion of forebrain NE terminals with 6-OHDA did not alter the PDR, consistent with a critical involvement of spinal noradrenergic fibers. The PDR was also decreased by phentolamine and prazosin, but not by propanolol, suggesting an involvement of α-adrenergic receptors in the response. This hypothesis was further supported by the finding that the efficacy of a variety of drugs (such as tricyclic antidepressants, phenothiazines, and antihypertensive compounds) for blocking the reflex was apparently related to their affinity for α-adrenergic receptors. Thus, the PDR is dependent on noradrenergic fibers in the spinal cord and may provide a simple screen for drugs with suspected α-adrenergic blocking properties or for agents that disrupt the function of central noradrenergic fibers.

Key words

Post-decapitation reflex Locus coeruleus Monoamines Alpha-noradrenergic Tricyclic antidepressants 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anden, N.-E., Corrodi, H., Fuxe, H., Hökfelt, T.: Evidence for a central 5-hydroxytryptamine receptor stimulation by lysergic acid diethylamide. Br. J. Pharmacol. 36, 1–7 (1968)Google Scholar
  2. Anderson, E. G.: Bulbospinal serotonin-containing nuerons and motor control. Fed. Proc. 31, 107–112 (1972)Google Scholar
  3. Bogdanski, D. F., Pletscher, A., Brodie, B. B., Udenfriend, S.: Identification and assay of serotonin in brain. J. Pharmacol. Exp. Ther. 117, 82–88 (1956)Google Scholar
  4. Bourn, W. M., Geiger, P. F., Jobe, P. C.: Influence of norepinephrine and 5-hydroxytryptamine in post decapitation convulsions in rats. Res. Commun. Psychol. Psychiat. Behav. 2, 9–20 (1977)Google Scholar
  5. Breese, G. R., Cooper, B. R.: Behavioral and biochemical interactions of 5,7-dihydroxytryptamine with various drugs when administered intracisternally to adult and developing rats. Brain Res. 98, 517–527 (1975)Google Scholar
  6. Breese, G. R., Cooper, B. R., Smith, R. D.: Biochemical and behavioral alterations following 6-hydroxydopamine administration into brain. In: Frontiers in catecholamine research. E. Usdin, S. Snyder, eds., pp. 701–706, 1973Google Scholar
  7. Breese, G. R., Kopin, I. J., Weise, V. K.: Effects of amphetamine derivatives on brain dopamine and noradrenaline. Br. J. Pharmacol. 38, 537–545 (1970)Google Scholar
  8. Breese, G. R., Traylor, T. D.: Effect of 6-hydroxydopamine on brain norepinephrine and dopamine: Evidence for selective degeneration of catecholamine neurons. J. Pharmacol. Exp. Ther. 174, 413–420 (1970)Google Scholar
  9. Breese, G. R., Traylor, T. D.: Depletion of brain noradrenaline and dopamine by 6-hydroxydopamine. Br. J. Pharmacol. 42, 88–99 (1972)Google Scholar
  10. Breese, G. R., Vogel, R. A., Mueller, R. A.: Biochemical and behavioral alterations in developing rats treated with 5,7-dihydroxytryptamine. J. Pharmacol. Exp. Ther. 205, 587–595 (1978)Google Scholar
  11. Clark, D. W. J., Laverty, R., Phelan, E. L.: Long-lasting peripheral and central effects of 6-hydroxydopamine in rats. Br. J. Pharmacol. 44, 233–243 (1972)Google Scholar
  12. Commissiong, J. W., Galli, C. L., Neff, N. H.: Differentiation of dopaminergic and noradrenergic neurons in rat spinal cord. J. Neurochem. 30, 1095–1099 (1978a)Google Scholar
  13. Commissiong, J. W., Hellstrom, S. O., Neff, N. H.: A new projection from Locus coeruleus to the spinal ventral columns: Histochemical and biochemical evidence. Brain Res. 148, 207–213 (1978b)Google Scholar
  14. Eichbaum, F. W., Slemer, O., Yasaka, W. J.: Post-decapitation convulsions and their inhibition by drugs. Exp. Neurol. 49, 808–812 (1975)Google Scholar
  15. Friedman, A. H.: Alteration of motor effects of acute decapitation by tremorine and other compounds. Fed. Proc. 23, 560 (1964)Google Scholar
  16. Fukuda, T., Araki, Y., Suenaga, N.: Inhibitory effects of 6-hydroxydopamine on the clonic convulsion induced by electroshock and decapitation. Neuropharmacology 14, 579–583 (1975)Google Scholar
  17. Greenslade, F. C., Scott, C. K., Chasin, M., Madison, S. M., Tobia, A. J.: Interaction of prazosin with alpha-adrenergic receptors — In vitro binding and in vivo antagonism. Biochem. Pharmacol. 28, 2409 (1979)Google Scholar
  18. Kamat, U. G., Sheth, U. K.: The role of central monoamine in decapitation convulsions in mice. Neuropharmacology 101, 571–579 (1971)Google Scholar
  19. Kanoff, P. D., Greengard, P.: Brain histamine receptors as targets for antidepressant drugs. Nature 272, 329–333 (1978)Google Scholar
  20. Laverty, R.: Is noradrenaline a mediator of motor function in the rat spinal cord? Proc. U. Otogo Med. Sch. 49, 32–34 (1971)Google Scholar
  21. Mason, S. T. and Fibiger, H. C.: Physiological function of descending noradrenaline projections to the spinal cord: Role in post-decapitation convulsions. Eur. J. Pharmacol. 57, 29–34 (1979)Google Scholar
  22. Myslinski, N. R., Thut, P. D.: The effect of 5,6-dihydroxytryptamine on post-decapitation convulsions. Life Sci. 21, 1475–1482 (1977)Google Scholar
  23. Pappas, B. A., Saari, M., Peters, D. A. V., Roberts, D. C. S., Fibiger, H. C.: Neonatal syntemic 6-hydroxydopamine and dorsal tegmental bundle lesion: Comparison of effects on CNS norepinephrine and the postdecapitation reflex. Brain Res. 155, 205–208 (1978)Google Scholar
  24. Richardson, J. S., Jacobowitz, D. M.: Depletion of brain norepinephrine by IV injection of 6-hydroxydopa: A biochemical, histochemical and behavioral study in rats. Brain Res. 58, 117–133 (1973)Google Scholar
  25. Roberts, D. C. S., Mason, S. T., Fibiger, H. C.: Selective depletion of spinal noradrenaline abolishes post-decapitation convulsions. Life Sci. 23, 2411–2414 (1978)Google Scholar
  26. Saari, M., Ings, R., Pappas, B. A.: Ontogeny of the post-decapitation convulsion in the rat: Effects of neonatal systemic 6-hydroxydopamine. Neuropharmacology 17, 873–877 (1978)Google Scholar
  27. Saari, M., Pappas, B. A.: Behavioral effects of neoanatal systemic 6-hydroxydopamine. Neuropharmacology 17, 863–871 (1978)Google Scholar
  28. Smith, R. D., Cooper, B. R., Breese, G. R.: Growth and behavioral changes in developing rats treated intracisternally with 6-hydroxydopamine: Evidence for involvement of brain dopamine. J. Pharmacol. Exp. Ther. 185, 609–619 (1973)Google Scholar
  29. Suenaga, N., Yamada, K., Fukuda, T.: Correlation between central catecholamine level and post-decapitation convulsion in rats treated with 6-hydroxydopamine. Brain Res. 122, 165–169 (1977)Google Scholar
  30. Thut, P. D., Myslinski, N. R.: The role of dopamine and serotonin in the prolongation of post-decapitation convulsions in mice. Life Sci. 19, 1569–1578 (1976)Google Scholar
  31. Titeler, M., Seeman, P.: Selective labeling of α-adrenergic receptors in caudate nucleus [3H]-dihydroergocryptine in the presence of spiperone blocked dopamine receptors. Proc. Natl. Acad. Sci. 75, 2249–2253 (1978)Google Scholar
  32. Tran, V. T., Chang, R. S. L., Snyder, S. H.: Histamine H1-receptors identified in mammalian brain with 3H-mepyramine. Proc. Natl. Acad. Sci. 75, 6290–6294 (1978)Google Scholar
  33. U'Prichard, D. C., Greenberg, D. A., Sheehan, P. P., Snyder, S. H.: Tricyclic antidepressants: Therapeutic properties and affinity for α-noradrenergic receptor binding sites in the brain. Science 199, 197–198 (1978)Google Scholar
  34. U'Prichard, D. C., Snyder, S. H.: Binding of 3H-catecholamines to α-noradrenergic receptor sites in calf brain. J. Biol. Chem. 252, 6450–6463 (1977)Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Bruce A. Pappas
    • 1
  • George R. Breese
    • 1
  • Richard B. Mailman
    • 1
  • Robert A. Mueller
    • 1
  1. 1.Departments of Psychiatry, Anesthesiology and Pharmacology, Biological Sciences Research Center, Child Development InstituteUniversity of North Carolina School of MedicineChapel HillUSA

Personalised recommendations