Summary
Chronic administration of antidepressants reduces brainβ-adrenergic receptor number and function. Peptide and steroid hormones are also capable of modifying receptor activity, and because circulating levels of these substances are altered in depressed patients, studies have been undertaken to determine whether hormones influence the neurochemical responses to antidepressant drugs. Co-administration of adrenocorticotropin (ACTH) and imipramine induces a more rapid reduction in brainβ-adrenergic receptor binding than is observed with either substance alone. Moreover, by itself, ACTH treatment alters the ability of norepinephrine to stimulate cAMP accumulation in brain tissue without affecting recognition site number. Lesioning of the dorsal noradrenergic bundle blocks the decline inβreceptor number and activity produced by the ACTH-imipramine treatment. Indeed, administration of ACTH facilitated the increase inβ-Preceptor number that occurs following denervation. These data indicate that ACTH treatment influencesβ-adrenergic receptor adaptations that occur in response to a change in synaptic activity. Such findings have implications in regard to the clinical responses to antidepressants, and the role of hormones in the etiology of affective illness.
Similar content being viewed by others
References
Banerjee, S. P., Kung, L. S., Riggi, S., Chanda, S. K.: Development ofβ-adrenergic receptor subsensitivity by antidepressants. Nature268, 455–456 (1977).
Bylund, D. B., Snyder, S. H.:β-Adrenergic binding in membrane preparations from mammalian brain. Mol. Pharmacol.12, 568–580 (1976).
Creese, I.: Receptor interactions of neuroleptics. In: Neuroleptics: Neurochemical, Behavioral and Clinical Pespectives (Coyle, J. T., Enna, S. J., eds.), pp. 183–222. New York: Raven Press. 1983.
Denber, H. C. B.: Pharmacotherapy of depression. In: Psychopharmacological Treatment-Theory and Practice (Denber, H. C. B., ed.), pp. 121–135. New York: Marcel Dekker. 1975.
DeWied, D.: Effects of peptide hormones on behavior. In: Frontiers in Neuroendocrinology (Ganong, W. G., Martini, L., eds.), pp. 97–140. London: Oxford University Press. 1969.
DeWied, D., Bohus, B.: Long-term and short-term effects on retention of a conditioned avoidance response in rats following treatment with long-acting pitressin andα-MSH. Nature212, 1484–1486 (1966).
Duman, R., Enna, S. J.: ACTH administration alters brainβ-adrenergic receptor affinity and function. Proc. Soc. Neurosci. (in press).
Duman, R. S., Andree, T., Kendall, D. A., Enna, S. J.: The effect of adrenocorticotropin administration onβ-adrenergic receptor adaptions in rat brain cerebral cortex. J. Neurochem. (in press).
Enna, S. J., Strada, S. J.: Post-synaptic receptors: recognition sites, ion channels and second messangers. In: Clinical Neurosciences (Rosenberg, R., Grossman, R., Schocket, S., Heinz, E.R., Willis, W., eds.). New York: Churchill Livingstone (in press).
Enna, S. J., Kendall, D. A.: Interaction of antidepressants with brain neurotransmitter receptors. J. Clin. Psychopharmacol.1, 12S-16S (1981).
Fuller, R. W.: Enhancement of monoaminergic neurotransmission by antidepressant drugs. In: Antidepressants: Neurochemical, Behavioral and Clinical Perspectives (Enna, S. J., Malick, J. B., Richelson, E., eds.), pp. 1–12. New York: Raven Press. 1981.
Kakiuchi, S., Rall, T. W.: The influence of chemical agents on the accumulation of adenosine 3′ 5′-phosphate in slices of rabbit cerebellum. Mol. Pharmacol.4, 367–378 (1968).
Kendall, D. A., Duman, R., Slopis, J., Enna, S. J.: Influence of adrenocortropin hormone and yohimbine on antidepressant-induced declines in rat brain neurotransmitter receptor binding and function. J.Pharmacol. Exp. Therap.222, 566–571 (1982 a).
Kendall, D. A., Stancel, G. M., Enna, S. J.: The influence of sex hormones on antidepressant-induced alterations in neurotransmitter receptor binding. J. Neurosci.2, 354–360 (1982 b).
Kendall, D. A., Stancel, G. M., Enna, S. J.: Imipramine: effect of ovarian steroids on modifications in serotonin receptor binding. Science211, 1183–1185 (1981).
Konig, J. F., Klippel, R. A.: The Rat Brain. Baltimore: Williams and Wilkins. 1962.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J.Biol. Chem.193, 265–275 (1951).
Mobley, P. L., Sulser, F.: Adrenal corticoids regulate the sensitivity of noradrenaline receptor-coupled adenylate cyclase in brain. Nature286, 608–609 (1980).
Olpe, H. R., Jones, R. S. G.: Excitatory effects of ACTH on noradrenergic neurons of the locus coerulus in the rat. Brain Res.251, 177–179 (1982).
Olsen, R. W., Enna, S. J.: GABA and anxiolytics. In: Anxiolytics: Neurochemical, Behavioral and Clinical Perspectives (Malick, J. B., Enna, S. J., Yamamura, H. I., eds.), pp. 55–76. New York: Raven Press. 1983.
Prange, A. J., Lipton, M. A., Nemeroff, C. B., Wilson, I. C.: The role of hormones in depression. Life Sci.20, 1305–1318 (1977).
Roberts, D. C., Bloom, F. E.: Adrenal steroid-induced changes inβ-adrenergic receptor binding in rat hippocampus. Europ. J. Pharmacol.74, 37–41 (1981).
Schildkraut, J. J.: The catecholamine hypothesis of affective disorders. A review of supporting evidence. Am. J. Psychiat.122, 509–522 (1965).
Shopsin, B., Wilk, S., Sathananthan, G., Gershon, S., Davis, K.: Catecholamines and affective disorders revised: A critical assessment. J. Nerv. Ment. Dis.158, 369–383 (1974).
Sulser, F. Janowsky, A. J., Okada, F., Manier, D. H., Mobley, P. L.: Regulation of recognition and action function of the norepinephrine (NE) receptorcoupled adenylate cyclase system in brain: implications for the therapy of depression, Neuropharmacology22, 425–531 (1983).
Sugrue, M. F.: Chronic antidepressant administration and adaptive changes in central monoaminergic systems. In: Antidepressants: Neurochemical, Behavioral and Clinical Perspectives (Enna, S. J., Malick J. B., Richelson, E., eds.), pp. 13–30. New York: Raven Press. 1981.
Vetulani, J., Sulser, F.: Actions of various antidepressant treatments reduce reactivity of noradrenergic cyclic AMP generating system in limbic forebrain. Nature257, 495–496 (1975).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Enna, S.J., Duman, R.S. β-adrenergic receptor regulation and antidepressants: The influence of adrenocorticotropin. J. Neural Transmission 57, 297–307 (1983). https://doi.org/10.1007/BF01249000
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01249000