Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-10T07:34:56.407Z Has data issue: false hasContentIssue false

The Benzodiazepine Receptor: The Pharmacology of Emotion

Published online by Cambridge University Press:  18 September 2015

H.A. Robertson*
Affiliation:
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia
*
Department of Pharmacology, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7
Rights & Permissions [Opens in a new window]

Summary:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Anxiety seems to be an inherent and perhaps necessary component of civilization. However, the biological basis of anxiety has always been as obscure as the definition of anxiety itself. The importance of anxiety to our mental wellbeing was noted by Freud (1933) who considered it a “nodalpoint”. As in the case of schizophrenia, there have been as many hypotheses to explain anxiety as there have been investigators with different techniques for studying it. The benzodiazepines, introduced clinically in I960, are now the most widely-used anxiolytic drugs. From the time of their introduction, it was felt that an explanation of the mode of action of benzodiazepines might shed considerable light on the basis of anxiety. The discovery, in 1977, of a specific benzodiazepine receptor, uniquely localized in the CNS, was the major turning point in this search (Squires and Braestrup, 1977; Mohler and Okada, 1977).

Type
Research Article
Copyright
Copyright © Canadian Neurological Sciences Federation 1980

References

REFERENCES:

Asano, T. and Spector, S. (1979). Identification of Inosine and hypoxanthine as endogenous ligands for the brain benzodia-zepine-binding sites. Proc. Natl. Acad. Sci. U.S.A. 75, 977981.CrossRefGoogle Scholar
Beer, B., Klepner, C.A., Lippa, A.S. and Squires, R.F. (1978). Enhancement of 3H-diazepam binding by SQ 65, 396: a novel anti-anxiety agent. Pharmacol. Biochem. Beh. 9, 849851.CrossRefGoogle ScholarPubMed
Braestrup, C. and Squires, R.F. (1978). Pharmacological characterization of Benzodiazepine Receptors in tlje Brain. European. J. Pharmacol. 48, 263270.CrossRefGoogle ScholarPubMed
Braestrup, C, Nielsen, M. and Olsen, CE. (1980). Urinary and brain β-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Proc. Natl. Acad. Sci. U.S.A. 77, 22882292.CrossRefGoogle ScholarPubMed
Braestrup, C, Neilsen, M., Nielsen, B. and Lyon, M. (1979). Benxodiazepine receptors in the brain as affected by different experimental stresses: The changes are small and not unidirectional. Psychopharmacology, 65, 273277.CrossRefGoogle Scholar
Broadhurst, P.L. (1975). The Maudsley reactive and non-reactive strains of rats: A Survey. Behavior Genetics, 5, 299319.CrossRefGoogle Scholar
Candy, J.C. and Martin, I.L. (1979). Distribution of muscimol and diazepam binding sites in the bovine cerebellar cortex. Proceedings 1st International Colloquim on Receptors neurotransmitters and peptide hormones. Capri, Italy, p. 123.Google Scholar
Costa, E. and Guidotti, A. (1979). Molecular mechanisms in the receptor action of benzodiazepines. Ann. Rev. Pharmacol. Toxicol. 19, 531545.CrossRefGoogle ScholarPubMed
Freud, S. (1933). Introductory lectures on psycho-analysis. G. Allen & Unwin. 2nd ed.Google Scholar
Henn, F.A. and Henke, D.J. (1978). Cellular localization of (3H)-diazepam receptors. Neuropharmacology, 17, 985988.CrossRefGoogle ScholarPubMed
Honecker, H. and Rommelspacher, H. (1978). Tetrahydronorharmane (Tetra-hydro-/β-carboline) a physiologically occurring compound of indole metabolism. Naunyn-Schmiedeberg’s Arch. Pharmacol. 305, 135141.CrossRefGoogle Scholar
Lippa, A.S., Klepner, C.A., Yunger, L., Sano, M.C, Smith, W.V. and Beer, B. (1978). Relationship between benzodiazepine receptors and experimental anxiety in rats. Pharmacol. Biochem. Beh. 9, 853856.CrossRefGoogle ScholarPubMed
Marks, G. and Lader, M. (1973). Anxiety states (anxiety neurosis): a review. J. Ner. Ment. Dis. 156, 318.CrossRefGoogle ScholarPubMed
McDonald, R. and Barker, J. (1978). Benzodiazepines specifically modulate GABA-mediated post-synaptic inhibition in cultured mammalian neurons. Nature, 271, 563564.CrossRefGoogle Scholar
Mohler, H. and Okada, T. (1977). Benzodiazepine Receptor: Demonstration in the Central Nervous System. Science, 198, 849851.CrossRefGoogle ScholarPubMed
Mohler, H., Polc, P., Cumin, R., Pieri, L. and Kettler, R. (1978). Nicotinamide is a brain constituent with benzodiazepine-like actions. Nature 278, 563565.CrossRefGoogle Scholar
Mohler, H., Battersby, M.K. and Richards, J.G. (1980). Benzodiazepine receptor protein identified and visualized in brain tissue by a photoaffinity label. Proc. Natl. Acad. Sci. U.S.A., 77, 16661670.CrossRefGoogle ScholarPubMed
Robertson, H.A. (1979). Benzodiazepine receptors in “emotional” and “non-emotional” mice: comparison of four strains. European J. Pharmacol. 56, 163166.CrossRefGoogle ScholarPubMed
Robertson, H.A., Martin, I.L. and Candy, J.M. Differences in benzodiazepine receptor binding in Maudsley reactive and Maudsley non-reactive rats. European J. Pharmacol. 50, 455457.CrossRefGoogle Scholar
Schlosser, W. and Franco, S. (1979). Reduction of y-aminobutyric acid (GABA)-mediated transmission by a convulsant benzodiazepine. J. Pharmacol. Exp. Therap. 211, 290295.Google Scholar
Shoemaker, D.W., Cummings, J.T. and Bidder, T.G. (1979). β-Carbolines in rat arcuate nucleus. Neuroscience 3, 233239.CrossRefGoogle Scholar
Soubrie, P., Thiebot, M.H., Jobert, A., Montastruc, J.L., Hery, F. and Hamon, M. (1980). Decreased convulsant potency of picrotoxin and pentetrazol and enhanced 3H-flunitrazepam cortical binding following stressful manipulations in rats. Brain Res. 189, 505517.CrossRefGoogle Scholar
Squires, R.F. and Braestrup, C. (1977). Benzodiazepine receptors in rat brain. Nature, 266, 732734.CrossRefGoogle ScholarPubMed
Tallman, J.F., Paul, S.M., Skolnick, P. and Gallager, D.W. (1980). Receptors for the age of anxiety: Pharmacology of the benzodiazepines. Science, 207, 274281.CrossRefGoogle ScholarPubMed
Wyatt, R.J., Erdelyi, E., Domaral, J.R., Elliot, G.R., Renson, J. and Barchas, J.D. (1975). Tryptoline formation by a preparation from brain with 5-methyltetrahydrofolic acid and tryptamine. Science 187, 853855.CrossRefGoogle Scholar
Young, W.S. III, and Kuhar, M.J. (1979). Autoradiographic localization of benzodiazepine receptor in the brains of humans and animals. Nature, 280, 393395.CrossRefGoogle Scholar
Zbinden, G. and Randall, L.O. (1967). Pharmacology of benzodiazepines: Laboratory and clinical correlations. Adv. Pharmacol. Chemother. 5, 213291.CrossRefGoogle ScholarPubMed