Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of ‘fear’-motivated behaviour

  • Sheila L. Handley
  • Siddika Mithani


An elevated X-maze with alternating open and enclosed arms was investigated as a model for the study of fear-induced behaviour. As predicted, the anxiolytics diazepam and amylobarbitone increased, and the putative anxiogenics ACTH and picrotoxin decreased the proportion of open arm entries. The α1-adrenoceptor agonists phenylephrine and ST587, and the α2-adrenoceptor antagonists idazoxan, piperoxane, RS-21361 and yohimbine decreased relative open-arm entries, thus resembling the putative anxiogenics. On the other hand, azepexole, clonidine and guanabenz, agonists at α2-adrenoceptors, and the α1-adrenoceptor antagonists prazosin and thymoxamine, enhanced the proportion of open arm entries at low doses, suggesting anxiolytic-like properties. A paradoxical fall in open arm entries occurred with these agents at higher doses. These results provide further evidence for the involvement of noradrenergic systems in ‘fear’-motivated behaviour.

Key words

Anxiety Central α-adrenoceptors Clonidine Exploratory activity ‘Fear’-motivated behaviour 


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  1. Baust W, Niemezyk H, Vieth J (1963) The action of blood pressure on the ascending reticular activating system with special reference to adrenaline induced arousal. Electroenceph Clin Neurophysiol 15:63–72Google Scholar
  2. Bradshaw CM, Stoker MJ, Szabadi E (1982) The effect of microelectrophoretically applied clonidine on single cerebral cortical neurones in the rat. Evidence for interaction with -α1-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 320:230–234Google Scholar
  3. Bugajski J, Zacyn E, Zdebska A (1980) The involvement of central adrenergic and histamine H2 receptors in the hypothermia induced by clonidine in the rat. Neuropharmacology 19:9–15Google Scholar
  4. Cavero J, Lefevre F, Roach AG (1977) Differential effects of prazosin in the pre- and postsynaptic α-adrenoceptors in the rat and dog. Br J Pharmacol 61:469PGoogle Scholar
  5. Charney DS, Heninger GR, Redmond Jr DE (1983) Yohimbine induced anxiety and increased noradrenergic functions in humans: Effects of diazepam and clonidine. Life Sciences 33:19–30Google Scholar
  6. Davis M, Astrachan DI (1981) Spinal modulation of acousticstartle: Opposite effects of clonidine and d-amphetamine. Psychopharmacology 75:219–225Google Scholar
  7. Davis M, Cedarbaum JM, Aghajanian GK, Gendelman DS (1977) Effects of clonidine on habituation and sensitization of acoustic startle in normal, decerebrate and LC lesioned rats. Psychopharmacology 51:243–253Google Scholar
  8. De Jonge A, van Meel JCA, Timmermans PBMWM, van Zweiten PA (1981) A lipophilic, selective α1-adrenoceptor agonist: 2-(2-chloro-5-trifluoromethyl phenylimino)imidazoline (St587). Life Sciences 28:2009–2016Google Scholar
  9. Dedek J, Scatton B, Zivkovic B (1981) Yohimbine blocks dopaminergic transmission in the rat striatum. Br J Pharmacol 73:239PGoogle Scholar
  10. Doxey JC, Roach AG, Smith CFC (1983) Studies on RX781094; a selective, potent and specific antagonist of α2-adrenoceptors. Br J Pharmacol 78:489–506Google Scholar
  11. Drew GM (1976) Effects of α-adrenoceptor agonists and antagonists on pre- and postsynaptically located α-adrenoceptors. Eur J Pharmacol 36:313–320Google Scholar
  12. File SE, Lister RG (1983) Anxiogenic action of picrotoxin and pentylenetetrazole: reversal by chlordiazepoxide. Br J Pharmacol 79:286PGoogle Scholar
  13. File SE, Vellucci SV (1978) Studies on the role of ACTH and of 5-HT in anxiety, using an animal model. J Pharm Pharmacol 30:105–110Google Scholar
  14. Goldenberg M, Snyder CH, Aranon Jr H (1947) New test for hypertension due to circulating epinephrine. JAMA 135:971–976Google Scholar
  15. Hoehn-Saric R, Merchant AF, Keyser MC, Smith VK (1981) Effects of clonidine on anxiety disorders. Arcj Gen Psychiatry 38:1278–1286Google Scholar
  16. Holmberg G, Gershon S (1961) Autonomic and psychic effects of yohimbine hydrochloride. Psychopharmacology 2:93–106Google Scholar
  17. Kruse H, Dunn RW, Theurer KL, Novick WJ, Shearman GT (1981) Attenuation of conflict induced suppression by clonidine: Indication of anxiolytic activity. Drug Dev Research 1:137–143Google Scholar
  18. Margolis R, Prieto P, Stein L, Chin S (1971) Statistical summary of 10,000 male cases using afrodex in the treatment of impotence. Current Therap Research 13:616–622Google Scholar
  19. Michel AD, Nahorski SR, Whiting RL (1981) Selectivity of RS21361 fo α2-adrenoceptors as determined by in vitro, in vivo and ligand binding studies. Br J Pharmacol 74:845 pGoogle Scholar
  20. Montgomery KC (1955) The relation between fear induced by novel stimulation and exploratory behaviour. J Comp Physiol Psychol 48:254–260Google Scholar
  21. Papeschi R, Sourkes TL, Youdim MBH (1971) The effect of yohimbine on brain serotonin metabolism, motor behaviour and body temperature of the rat. Eur J Pharmacol 15:318–326Google Scholar
  22. Redmond DE, Huang YH (1979) Current concepts II: New evidence for a locus coeruleus-norepinephrine connection with anxiety. Life Sciences 25:2149–2162Google Scholar
  23. Soffer A (1954) Rogitine and benodaine in the diagnosis of phaeochromocytoma. Med Clin North America 38:374–384Google Scholar
  24. Starke K, Borowski E, Endo T (1975) Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Eur J Pharmacol 34:385–388Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • Sheila L. Handley
    • 1
  • Siddika Mithani
    • 1
  1. 1.Pharmacology Laboratories, Department of PharmacyUniversity of AstonBirminghamUK

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