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α1- and β-adrenoceptor stimulation potentiate the anticonflict effect of a benzodiazepine

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Summary

Interactions between different noradrenaline (NA)-active drugs and the benzodiazepine alprazolam (APZ) were examined in a modified Vogel's drinking conflict test in the rat. In a dose (0.5mg/kg) which did not alter the behavior by itself, the α2-adrenoceptor antagonist yohimbine consistently was found to enhance the anticonflict effect of APZ (0.5mg/kg). The yohimbine induced potentiation of the APZ effect was counteracted both by the selective α1-adrenoceptor antagonist prazosin (0.25mg/kg) and the β-adrenoceptor antagonist propranolol (2.0mg/kg), but not by the selective β1-adrenoceptor antagonist metoprolol (2.0 mg/kg). Similar potentiating phenomena were obtained after co-administration of APZ (0.5 mg/kg) with the selective α1-adrenoceptor agonist ST 587 (0.5–1.0 mg/kg) as well as with the suggested β2-adrenoceptor agonist clenbuterol (1.0 mg/kg). The results indicate that the potentiative effects of α2-adrenoceptor antagonists on BDZ induced anticonflict action may be due to increased stimulation of α1 and β-adrenoceptors,via enhanced NA release. The findings are discussed in relation to the signal-to-noise hypothesis of NA function, and in relation to the suggested NA involvement in anxiety-related behavior.

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References

  • Åblad B, Carlsson E, Ek L (1973) Pharmacological studies of two new cardioselective adrenergic beta-receptor antagonists. Life Sci 12: 107–119

    Google Scholar 

  • Baraban JM, Wang RY, Aghajanian GK (1978) Reserpine suppression of dorsal raphe neuronal firing: mediation by adrenergic system. Eur J Pharmacol 52: 27–36

    Google Scholar 

  • Baraban JM, Aghajan GK (1980) Suppression of serotonergic neuronal firing by α-adrenoceptor antagonists: evidence against GABA mediation. Eur J Pharmacol 66: 287–294

    Google Scholar 

  • Cedarbaum JM, Aghajanian GK (1976) Noradrenergic neurons of the locus coeruleus: inhibition by epinephrine and activation by the alpha-antagonist piperoxane. Brain Res 112: 413–419

    Google Scholar 

  • Cedarbaum JM, Aghajanian GK (1977) Catecholamine receptors on the locus coeruleus neurons: pharmacological characterization. Eur J Pharmacol 44: 375–385

    Google Scholar 

  • Charney DS, Heninger GR, Redmond DE Jr (1983) Yohimbine induced anxiety and increased noradrenergic function in humans: effects of diazepam and clonidine. Life Sci 33: 19–29

    Google Scholar 

  • Charney DS, Heninger GR, Breier A (1984) Noradrenergic function in panic anxiety: effects of yohimbine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry 41: 751–763

    Google Scholar 

  • Charney DS, Woods SW, Goodman WK, Heninger GR (1987) Neurobiological mechanisms of panic anxiety: biochemical and behavioral correlates of yohimbine-induced panic attacks. Am J Psychiatry 144: 1030–1036

    Google Scholar 

  • Corda MG, Blaker WD, Mendelson WB, Guidotti A, Costa E (1983) Beta-carbolines enhance shock-induced suppression of drinking in rats. Proc Natl Acad Sci USA 80: 2072–2076

    Google Scholar 

  • Cowen PJ, Grahame-Smith DG, Green AR, Heal DJ (1982) β-adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses. Br J Pharmacol 76: 265–270

    Google Scholar 

  • Cowen PJ, Fraser S, Grahame-Smith DG, Green AR, Stanford S (1983) The effect of chronic antidepressant administration on β-adrenoceptor function of the rat pineal. Br J Pharmacol 78: 89–96

    Google Scholar 

  • Crow TJ, Deakin JFW, File SE, Longden A, Wendlandt S (1978) The locus coeruleus noradrenergic system-evidence against a role in attention, habituation, anxiety and motor activity. Brain Res 155: 249–261

    Google Scholar 

  • De Jonge A, Van Meel JCA, Timmermans PBMWM, Van Zwieten PA (1981) A lipophilic, selective α1-adrenoceptor agonist: 2-(2-chloro-5-trifluoromethylphenylimino)-imidazolidine (St 587). Life Sci 28: 2009–2016

    Google Scholar 

  • Dorow R, Horowski R, Paschelke G, Amin M (1983) Severe anxiety induced by FG7142, a β-carboline ligand for benzodiazepine receptors. Lancet 2: 98–99

    Google Scholar 

  • Engel JA, Hjorth S, Svensson K, Carlsson A, Liljequist S (1984) Anticonflict effect of the putative serotonin receptor agonist 8-hydroxy-2-(Dl-n-propylamino)tetralin (8-OH-DPAT). Eur J Pharmacol 105: 365–368

    Google Scholar 

  • Engelhardt G (1976) Pharmakologisches Wirkungsprofil von NAB 365 (Clenbuterol), einem neuen Broncholytikum mit einer selektiven Wirkung auf die adrenergen β2-Rezeptoren. Arzneimittelforsch 26: 1404–1420

    Google Scholar 

  • Gallager DW, Aghajanian GK (1976) Effect of antipsychotic drugs on the firing of dorsal raphe cells. I. Role of adrenergic system. Eur J Pharmacol 39: 341–355

    Google Scholar 

  • Goldberg MR, Robertson D (1983) Yohimbine: a pharmacological probe for study of the α2-andrenoreceptor. Pharmacol Rev 35: 143–180

    Google Scholar 

  • Grant SJ, Huang YH, Redmond Jr DE (1980) Benzodiazepines attenuate single unit activity in the locus coeruleus. Life Sci 27: 2231–2236

    Google Scholar 

  • Hallberg H (1986) Pharmacological identification of a functional β2-adrenoceptor in the rat brain. Thesis, University of Göteborg

  • Handley SL, Mithani S (1984) Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of “fear”-motivated behaviour. Naunyn-Schmiedebergs Arch Gen Pharmacol 327: 1–5

    Google Scholar 

  • Hoehn-Saric R (1982) Neurotransmitters in anxiety. Arch Gen Psychiatry 39: 735–742

    Google Scholar 

  • Holmberg G, Gershon S (1961) Autonomic and psychic effects of yohimbine hydrochloride. Psychopharmacologia 2: 93–106

    Google Scholar 

  • Kahn RS, van Praag HM, Wetzler S, Asnis GM, Barr G (1988) Serotonin and anxiety revisited. Biol Psychiatry 23: 189–208

    Google Scholar 

  • Koob GF, Thatcher-Britton K, Britton DR, Roberts DS, Bloom FE (1984) Destruction of the Locus Coeruleus or the dorsal NE bundle does not alter the release of punished responding by ethanol and chlordiazepoxide. Physiol Behav 33: 479–485

    Google Scholar 

  • Kruse H, Dunn RW, Theurer KL, Novick WJ, Shearman GT (1981) Attenuation of conflictinduced supression by clonidine: indication of anxiolytic activity. Drug Dev Res 1: 137–143

    Google Scholar 

  • Modigh K (1987) Antidepressant drugs in anxiety disorders. Acta Psychiatr Scand 76 [Suppl 335]: 57–71

    Google Scholar 

  • Nimgaonkar VL, Green AR, Cowen PJ, Heal DJ, Grahame-Smith DG, Deakin JFW (1983) Studies on the mechanisms by which clenbuterol, a β-adrenoceptor agonist, enhances 5-HT-mediated behaviour and increases metabolism of 5-HT in the brain of the rat. Neuropharmacology 22: 739–749

    Google Scholar 

  • Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24: 525–529

    Google Scholar 

  • Petersen EN, Jensen LH, Honore T, Braestrup C (1983) Differential pharmacological effects of benzodiazepine receptor inverse agonists. In: Biggio G, Costa E (eds) Benzodiazepine recognition site ligands: biochemistry and pharmacology. Raven Press, New York

    Google Scholar 

  • Redmond Jr DE, Huang YH (1979) Current concepts II. New evidence for a locus coeruleusnorepinephrine connection with anxiety. Life Sci 25: 2149–2162

    Google Scholar 

  • Sanghera MK, German DC (1983) The effects of benzodiazepine and non-benzodiazepine anxiolytics on locus coeruleus unit activity. J Neural Transm 57: 267–279

    Google Scholar 

  • Sepinwall J, Cook L (1981) Neuropharmacology of clonidine-preclinical aspects. Studies on clonidine in animal tests for anti-anxiety activity. Psychopharmacol Bull 17: 24–26

    Google Scholar 

  • Söderpalm B, Engel JA (1988) Biphasic effects of clonidine on conflict behavior; involvement of different alpha-adrenoceptors. Pharmacol Biochem Behav 30: 471–477

    Google Scholar 

  • Söderpalm B, Engel JA (1989) α2-Adrenoceptor antagonists potentiate the anticonflict and the rotarod impairing effects of benzodiazepines. J Neural Transm 76: 191–204

    Google Scholar 

  • Söderpalm B, Eriksson E, Engel JA (1989 a) Anticonflict and rotarod impairing effects of alprazolam and diazepam in rat after acute and subchronic administration. Progr Neuropsychopharmacol Biol Psychiatry 13: 269–283

    Google Scholar 

  • Söderpalm B, Hjorth S, Engel JA (1989 b) Effects of 5-HT1A receptor agonists and L-5- HTP in Montgomery's conflict test. Pharmacol Biochem Behav 32: 259–265

    Google Scholar 

  • Svensson TH, Bunney BS, Aghajanian GK (1975) Inhibition of both noradrenergic and serotonergic neurons in the brain by the α-adrenergic agonist clonidine. Brain Res 92: 291–306

    Google Scholar 

  • Thiébot M-H, Soubrié Ph, Doare L, Simon P (1984) Evidence against the involvement of a noradrenergic mechanism in the release by diazepam of novelty-induced hypophagia in rats. Eur J Pharmacol 100: 201–205

    Google Scholar 

  • Thiébot M-H, Soubrié Ph, Sanger D (1988) Anxiogenic properties of beta-CCE and FG7142: a review of promises and pitfalls. Psychopharmacology 94: 452–463

    Google Scholar 

  • Treit D (1985) Animal models for the study of anti-anxiety agents: a review. Neurosci Behav Rev 9: 203–222

    Google Scholar 

  • Waldmeier PC (1981) Stimulation of serotonin turnover by β-adrenoceptor agonists. Naunyn Schmiedebergs Arch Pharmacol 317: 115–119

    Google Scholar 

  • Waterhouse BD, Moises HC, Woodward DJ (1981) Alpha-receptor-mediated facilitation of cortical neuronal respones to excitatory synaptic inputs and iontophoretically applied acetylcholine. Neuropharmacology 20: 907–920

    Google Scholar 

  • Weiner N (1980) Drugs that inhibit adrenergic nerves and block adrenergic receptors. In: Goodman Gilman A, Goodman LS, Gilman A (eds) Goodman Gilman's The Pharmacological Basis of Therapeutics. Macmillan, New York, pp 176–210

    Google Scholar 

  • Woodward DJ, Moises HC, Waterhouse BD, Hoffer BJ, Freedman R (1979) Modulatory actions of norepinephrine in the central nervous system. Fed Proc 38: 2109–2116

    Google Scholar 

  • Yeh HH, Woodward DJ (1983) Beta-1 adrenergic receptors mediate noradrenergic facilitation of purkinje cell responses to gamma-aminobutyric acid in cerebellum of the rat. Neuropharmacology 22: 629–639

    Google Scholar 

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  1. B. Söderpalm

    Present address: Department of Pharmacology, University of Göteborg, Göteborg, Sweden

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  1. Department of Pharmacology, University of Göteborg, Göteborg, Sweden

    J. A. Engel

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Söderpalm, B., Engel, J.A. α1- and β-adrenoceptor stimulation potentiate the anticonflict effect of a benzodiazepine. J. Neural Transmission 79, 155–167 (1990). https://doi.org/10.1007/BF01245127

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  • DOI: https://doi.org/10.1007/BF01245127

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