Benzodiazepine receptor-mediated experimental ‘anxiety’ in rhesus monkeys after infusion of 3-carboethoxy-ß-carboline (ß-CCE)

  • Steven M. Paul
  • Philip Ninan
  • Thomas Insel
  • Phil Skolnick


The presence of specific recognition (viz. receptor) sites for benzodiazepines in brain that are functionally (and perhaps structurally) coupled to both recognition sites for γ-aminobutyric acid (GABA) and a chloride ionophore has been firmly established (cf. Tallman et al., 1980; Paul et al., 1981; Skolnick and Paul, 1982). Both direct and indirect evidence suggest that this ‘supramolecular complex’ mediates the pharmacological actions of benzodiazepines as well as other structurally unrelated compounds which share common properties with the benzodiazepines (Paul et al., 1981; Skolnick and Paul, 1982). Whether this supramolecular complex has a physiological role in the absence of an exogenous ligand (drug) has been a source of considerable speculation, particularly regarding its function in the pathophysiology of anxiety and related disorders (cf. Paul and Skolnick, 1981).


Rhesus Monkey Plasma Cortisol Acid Ethyl Ester Plasma Cortisol Level Exogenous Ligand 
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  1. Braestrup, C., Nielsen, M. and Olsen, C. (1980). Urinary and brain β-carboline–3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Proc. Natl Acad. Sci. USA, 77, 2288–92PubMedCentralCrossRefPubMedGoogle Scholar
  2. Braestrup, C., Schmiechen, R., Neef, G., Nielsen, M. and Petersen, E. (1982). Interaction of convulsive ligands with benzodiazepine receptors. Science, 216, 1241–3CrossRefPubMedGoogle Scholar
  3. Cowen, P., Green, A., Nutt, D. and Martin, I. (1981). Ethyl-β-carboline–3-carboxylate lowers seizure threshold and antagonizes flurazepam-induced sedation in rats. Nature, 290, 54–5CrossRefPubMedGoogle Scholar
  4. File, S. (1982). Animal anxiety and the effects of benzodiazepines. In Pharmacology of Benzodiazepines (ed. S. Paul, P. Skolnick, J. Tallman and E. Usdin), Macmillan, London, in pressGoogle Scholar
  5. Hunkeler, W., Mohler, H., Pieri, L., Polc, P., Bonetti, E., Cumin, R., Schaffner, R. and Haefely, W. (1981). Selective antagonists of benzodiazepines. Nature, 290, 514–16CrossRefPubMedGoogle Scholar
  6. Mendelson, W., Cain, M., Cook, J., Paul, S. and Skolnick, P. (1982). Do benzodiazepine receptors plays a role in sleep regulation: studies with the benzodiazepine antagonist, 3-hydroxymethyl-β-carboline (3-HMC). In Beta-Carbolines and Tetra-isoquinolines (ed. E. Usdin), Alan R. Liss, New York, in pressGoogle Scholar
  7. Paul, S., Marangos, P. and Skolnick, P. (1981). The benzodiazepine-GABA receptor chloride ionophore complex: common site of minor tranquilizer action. Biol. Psychiat., 16, 213–29PubMedGoogle Scholar
  8. Paul, S. and Skolnick, P. (1981). Benzodiazepine receptors and psychopathological states: towards a neurobiology of anxiety. In Anxiety: New Research and Changing Concepts (ed. D. Klein and J. Rabkin), Raven Press, New York, pp. 215–33Google Scholar
  9. Schweri, M., Cain, M., Cook, J., Paul, S. and Skolnick, P. (1982). Blockade of 3-carbomethoxy-β-carboline induced seizures by diazepam and the benzodiazepine antagonists Ro 15–1788 and CGS 8216. Pharmacol., Biochem. Behav., in pressGoogle Scholar
  10. Skolnick, P., Lock, K.-L., Paugh, B., Marangos, P., Windsor, R. and Paul, S. (1980). Pharmacologic and behavioral effects of EMD 28422: a novel purine which enhances [3H]diazepam binding to brain benzodiazepine receptors. Pharmacol., Biochem. Behav., 12, 685–9CrossRefGoogle Scholar
  11. Skolnick, P. and Paul, S. (1982). Molecular pharmacology of the benzodiazepines. Int. Rev. Neurobiol., 23, 103–40CrossRefPubMedGoogle Scholar
  12. Skolnick, P., Schweri, M., Kutter, E., Williams, E. and Paul, E. (1982). Inhibition of [3H]diazepam and 3-carboethoxy-β-carboline binding by irazepine: evidence for binding to different ‘domains’ of the benzodiazepine receptor. J. Neurochem., in pressGoogle Scholar
  13. Tallman, J., Paul, S., Skolnick, P. and Gallager, D. (1980). Receptors for the age of anxiety: molecular pharmacology of the benzodiazepines. Science, 207, 274–81CrossRefPubMedGoogle Scholar
  14. Tenen, S. and Hirsch, J. (1980). β-Carboline–3-carboxylic acid ethyl ester antagonizes diazepam activity. Nature, 288, 609–10CrossRefPubMedGoogle Scholar

Copyright information

© The contributors 1983

Authors and Affiliations

  • Steven M. Paul
    • 1
  • Philip Ninan
    • 1
  • Thomas Insel
    • 2
  • Phil Skolnick
    • 3
  1. 1.Clinical Neuroscience BranchNIMH, National Institutes of HealthBethesdaUSA
  2. 2.Clinical Neuropharmacology BranchNIMH, National Institutes of HealthBethesdaUSA
  3. 3.Laboratory of Bioorganic ChemistryNIADDK, National Institutes of HealthBethesdaUSA

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