Skip to main content
Log in

Effects of Chronic Administration of Interferon α A/D on Serotonergic Receptors in Rat Brain

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The effects of chronic administration of interferon (IFN; recombinant human IFN -αA/D) on serotonergic binding sites in rat brain were investigated. IFN was injected daily for 2 weeks at a dose of 100000 I.U./kg, (i.p.) in male Wistar rats. IFN did not alter either [3H]ketanserin binding to 5-HT2A receptors or [3H]paroxetine binding to 5-HT transporters. Scatchard analysis of [3H]8-hydroxy-dipropylaminotetraline (8-OH-DPAT) binding to 5-HT1A receptors demonstrated the presence of high- and low-affinity binding sites in both treatment and control groups. IFN significantly increased both Kd and Bmax measures of [3H]8-OH-DPAT binding at low-affinity binding sites, but not at the high-affinity sites. These results suggest that IFN affects the low-affinity 5-HT1A receptors sites and may be involved in the development of IFN-induced psychiatric disturbances.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Renault, R. P., Hoognagle, J. H., Park, Y., Mullen, K. D., Peters, M., Jones, B., Rustgi, V., and Jones, A. 1987. Psychiatric complications of long-term interferon alpha therapy. Arch. Intern. Med. 147:1577–1580.

    Google Scholar 

  2. McDonald, E. M., Mann, A. H., and Thomas, H. C. 1987. Interferon as mediators of psychiatric morbidity. Lancet, 21:1175–1178.

    Google Scholar 

  3. Levenson, J. A., and Fallon, H. J. 1993. Fluoxetine treatment of depression caused by interferon-α. Am. J. Gastroenter., 88:760–761.

    Google Scholar 

  4. Roosth, J., Richard, B., Pollard, S., Brown, L. and Meyer, W. J. 1986. Cortisol stimulation by recombinant interferon-α2. J. Neuroimm., 12:311–316.

    Google Scholar 

  5. Meyers, C. A., Scheibel, R. S., and Forman, A. D. 1991. Persistent neurotoxicity of systemically administrated interferon-alpha. Neurology, 41:672–676.

    Google Scholar 

  6. Müller, H., Hammes, E, Hiemke, C., and Hess, G. 1991. interferon-alpha-2-induced stimulation of ACTH and cortisol secretion in man. Neuroendocrinology, 54:499–503.

    Google Scholar 

  7. Kidron, D., Saphier, D., Ovadia, H., Weidenfireld, J., and Abramsky, O. 1989. Central administration of immunomodulatory factors alters neural activity and adrenocortical secretion. Brain Behav. Immun. 3:15–27.

    Google Scholar 

  8. Segall, M. A., and Crnic, L. S. 1990. An animal model for the behavioral effects of interferon. Behav. Neurosci., 104:612–618.

    Google Scholar 

  9. Dunn, A. L., and Crnic, L. S. 1993. Repeated injection of interferon-αA/D in Balb/c mice: behavioral effects. Brain Behav. Immun., 7:104–111.

    Google Scholar 

  10. Saphier, D., Welch, J. E., and Chuluyan, H. E. 1993. α-Interferon inhibits adrenocortical secretion via μ1-Opioid receptors in the rat. Eur. J. Pharmacol., 236:183–191.

    Google Scholar 

  11. Saphier, D., Roerig, S. C., Ito, C., Vlasak, W. R., Farrar, G. E., Broyles, J. E., and Welch, J. E. 1994. Inhibition of neural and neuroendocrine activity by α-interferon: neuroendocrine, electrophysiological, and biochemical studies in the rat. Brain Behav. Immun., 8:37–56.

    Google Scholar 

  12. Farkkila, M., Iivanainen, M., Harkonen, M., Laakso, J., Mattson, K., Niiranen, A., Larson, T. A., and Cantell, K. 1988. Effect of interferon-γ on biogenic amine metabolism, electroencephalographic recordings, and transient potentials. Clin. Neuropharm. 11:63–67.

    Google Scholar 

  13. Habif, D. V., Lipton, R. and Cantell, K. 1975. Interferon crosses blood-cerebrospinal fluid barrier in monkeys. Proc. Soc. Exp. Biol. Med., 149:287–289.

    Google Scholar 

  14. Greig, N. H., Soncrant, T. T., Wozniak, K. M. and Rapoport, S. I. 1988. Plasma and tissue pharmacokinetics of human interferonalpha in the rat after its intravenous administration. J. Pharmacol. Exp. Ther., 245:574–580.

    Google Scholar 

  15. Wiranowska, M., Wilson, T. C., Thompson, K. and Prockop, L. D. 1989. Cerebral interferon entry in mice after osmotic alteration of blood-brain barrier. J. Interferon Res., 9:353–362.

    Google Scholar 

  16. Janicki P. K. 1992. Binding of human alpha-interferon in the brain tissue membranes of rat. Res. Commun. Chem. Pathol. Pharmacol., 75:117–120.

    Google Scholar 

  17. Menzies, R. A., Patel, R., Hall, N. R. S., O'Grady, M. P., and Rier, S. E. 1992. Human recombinant interferon alpha inhibits naloxone binding to rat brain membranes. Life Sci. 50:227–232.

    Google Scholar 

  18. Pazos, A., Hoyer, D., and Palacios, J. M. 1984. Mesulergine, a selective serotonin-2 ligand in the rat cortex: evidence for species differences in brain serotonin-2 receptors. Eur. J. Pharmacol. 106:531–538.

    Google Scholar 

  19. Hall, M. D., Mestikawy, S. El., Emerit, M. B., Pichat, L., Hamon, M., and Gozlan, H. 1985. [3H]8-Hydroxy-2-(Di-n-Propylamino)tetralin binding to pre-and postsynaptic 5-hydroxytryptamine sites in various regions of the rat brain. J. Neurochem., 44:1685–1696.

    Google Scholar 

  20. Habert, E., Graham, D., Taharaoui, L., Claustra, Y., and Langer, S. Z. 1985. Characterization of [3H]paroxetine binding to rat cortical membranes. Eur. J. Pharmacol., 118:107–114.

    Google Scholar 

  21. Lowry, O. H., Rosenbough, M. J., Farr, A. C., and Randell, R.J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193:265–275.

    Google Scholar 

  22. Munson, P. J. and Rodbard, D. 1980. LIGAND: a versatile computerized approach for the characterization of ligand binding systems. Anal. Biochem., 107:220–239.

    Google Scholar 

  23. Goodnough, D. B., and Baker, G. B. 1994. 5-Hydrotryptamine 2 and β-adrenergic receptor regulation in rat brain following chronic treatment with desipramine and fluoxetine alone and in combination. J. Neurochem., 62:2262–2268.

    Google Scholar 

  24. Gleiter, C. H., and Nutt, D. J. 1988. Repeated electroconvulsive shock does not change [3H]-paroxetine binding to the 5-HT uptake site in rat cortical membranes. Psychopharmacology, 95:68–70.

    Google Scholar 

  25. Sprouse, J. S., Aghajanian, G. K. 1987. Electrophysiological response of serotonergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonist. Synapse, 1:3–9.

    Google Scholar 

  26. Nénonéné, E. K., Radja, F., Carli, M., Grondin, L., and Reader, A. 1994. Heterogeneity of cortical hippocampal 5-HT1A receptors: a reappraisal of homogenate binding with 8-[3H]hydroxydipropylaminotetralin. J. Neurochem., 62:1822–1834.

    Google Scholar 

  27. Lovenberg, T. W., Baron, B. M., de-Lecea, L., Miller, D., Prosser, R. A., Rea, M. A., Foye, P. E., Racke, M., Slone, A. L., Siegel, B. W., Danielson, P. E., Sutcliffe, J. G., and Erlander, M. G. 1993. A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron, 11:449–458.

    Google Scholar 

  28. Ruat, M., Traiffort, E., Leurs, R., Tardivel-Lacombe, J., Diaz, J., Arrang, J. M., and Schwartz, J. C. 1993. Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation. Proc. Natl. Acad. Sci. USA, 90:8547–51.

    Google Scholar 

  29. Hrdina, P. D., Demeter, E., Vu, T. B., Sotonyi, P., and Palkovits, M. 1993. 5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: increase in 5-HT2 sites in cortex and amygdala. Brain Res., 614:37–44.

    Google Scholar 

  30. Pacheco, M. A., Stockmeier, C., Meltzer, H. Y., Overholser, J. C., Dilley, G. E., and Jope, R. S. 1996. Alterations in phosphoinositide signaling and G-protein levels in depressed suicide brain. Brain Res., 723:37–45.

    Google Scholar 

  31. Brunner, J. D., Innis, R. B., Salomon, R. M., Staib, L. H., Ng, C. K., Miller, H. L., Bronen, R. A., Krystal J. H., Duncan, J., Rich, D., Price, L. H., Malison, R., Dey, H., Soufer, R., and Charney, D. S. 1997. Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse. Arch. Gen. Psychiatry, 54:364–374.

    Google Scholar 

  32. Gustafson, E. L., Durkin, M. M., Bard, J. A., Zgombick, J. and Branchek, T. A. 1996. A receptor autoradiographic and in situ hybridization analysis of the distribution of the 5-ht7 receptor in rat brain. Br. J. Pharmacol., 117:657–666.

    Google Scholar 

  33. Shimizu, S., Nishida, A., Zensho, H. and Yamawaki, S. 1996. Chronic antidepressants exposure enhances 5-hydroxytryptamine7 receptor-mediated cyclic adenosine monophosphate accumulation in rat frontocortical astrocytes. J. Pharmacol. Exp. Ther., 279:1551–1558.

    Google Scholar 

  34. Roth, B. L., Craigo, S. C., Choudhary, M. S., Uluer, A., Monsma, F. J. Jr., Shen, Y., Meltzer, H. Y., Sibley, D. R. 1994. Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J. Pharmacol. Exp. Ther., 268:1403–1410.

    Google Scholar 

  35. D'Urso, R., Falaschi, P., Canfalone, G., Carusi, E., Proietti, A., Barnaba, V., and Balsano, F. 1991. Neuroendocrine effects of recombinant α-interferon administration in humans. Prog. Neuroendocrin Immunonol., 4:20–25.

    Google Scholar 

  36. Kathol, R. G., Jaeckle, R. S., Lopez, J. F., and Meller, W. H. 1989. Pathophysiology of HPA axis abnormalities in patients with major depression: an update. Am. J. Psychiatry, 146:311–317.

    Google Scholar 

  37. Corre, S. Le., Sharp, T., Young, A. H., and Harrison, P. J. 1997. Increase of 5-HT7(serotonin-7) and 5-HT1A(serotonin-1A) receptor mRNA expression in rat hippocampus after adrenalectomy. Psychopharmacology, 130:368–374.

    Google Scholar 

  38. Yau, J. L. W., Noble, J., Widdowson, J., and Seckl, J. R. 1997. Impact of adrenalectomy on 5-HT6 and 5-HT7 receptor gene expression in the rat hippocampus. Mol. Brain Res., 45:182–186.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abe, S., Hori, T., Suzuki, T. et al. Effects of Chronic Administration of Interferon α A/D on Serotonergic Receptors in Rat Brain. Neurochem Res 24, 359–363 (1999). https://doi.org/10.1023/A:1020929415443

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020929415443

Navigation