Abstract
Clonidine (10–40 μg/kg) produced a dosedependent reduction of fear as measured by the potentiated startle effect (increased acoustic startle in the presence of a cue which had been previously paired with shock). The reduction of potentiated startle could not be accounted for entirely by a general depressant effect of clonidine on startle nor by an acceleration of extinction. Piperoxane and yohimbine, which are associated with anxiety in humans, increased potentiated startle, whereas propranolol and WB-4101 did not. These results provide further evidence that the potentiated startle paradigm in the rat is sensitive to drugs that alter anxiety in humans. Moreover, they support the hypothesis that norepinephrine transmission is important for the expression of fear or anxiety.
Similar content being viewed by others
References
Andén, N. E., Corrodi, H., Fuxe, K., Hokfelt, B., Hokfelt, T., Rydin, C. Svensson, T.: Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci. 9, 513–523 (1970)
Andén, N. E., Grabowska, M., Ströbom, U.: Different alphaadrenoceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn Schmiedebergs Arch. Pharmacol. 292, 43–52 (1976)
Andén, N. E., Ströbom, U.: Adrenergic receptor blocking agents: Effects on central noradrenaline and dopamine receptors and on motor activity. Psychopharmacologia (Berl.) 38, 91–103 (1974)
Baraban, J. M., Aghajanian, G. K.: Alpha-adrenoceptor mediation of adrenergic-serotonergic interactions in dorsal raphe. Neurosci. Abstr. 4, 267 (1978)
Berthelsen, S., Pettinger, W. A.: A functional basis for classification of α-adrenergic receptors. Life Sci. 21, 595–606 (1977)
Bird, S. J., Kuhar, M. J.: Iontophoretic applications of opiates to the locus ceruleus. Brain Res. 122, 523–533 (1977)
Borowski, E., Starke, K., Ehrl, H., Endo, T.: A comparison of pre-and post-synaptic effects of α-adrenolytic drugs in the pulmonary artery of the rabbit. Neurosci. Abstr. 2, 285–296 (1977)
Brown, J. S., Kalish, H. I., Farber, I. E.: Conditioned fear as revealed by magnitude of startle response to an auditory stimulus. J. Exp. Psychol. 41, 317–327 (1951)
Cedarbaum, J. M., Aghajanian, G. K.: Noradrenergic neurons of the locus coeruleus: Inhibition by epinephrine and activation by the α-antagonist piperoxane. Brain Res. 112, 413–420 (1976)
Cedarbaum, J. M., Aghajanian, G. K.: Catecholamine receptors on locus coeruleus neurons: Pharmacological characterization. Eur. J. Pharmacol. 44, 375–385 (1977)
Chi, C. C.: The effect of amobarbital sodium on conditioned fear as measured by the potentiated startle response in rats. Psychopharmacologia (Berl.) 7, 115–122 (1965)
Crow, T. J., Deakin, J. F. W., File, S. E., Longden, A., Wendlandt, S.: The locus coeruleus noradrenergic system: Evidence against a role in attention, habituation, anxiety and motor activity. Brain Res. 155, 249–261 (1978)
Davis, M.: Diazepam and flurazepam: Effects on conditioned fear as measured with the potentiated startle paradigm. Psychopharmacology 62, 1–7 (1979a)
Davis, M.: Morphine and naloxone: Effects on conditioned fear as measured with the potentiated startle paradigm. Eur. J. Pharmacol. 54, 341–347 (1979b)
Davis, M., Astrachan, D. I.: Conditioned fear and startle magnitude: Effects of different footshock and backshock intensities in training. J. Exp. Psychol. (Anim. Behav.) 4, 95–103 (1978)
Davis, M., Cedarbaum, J. M., Aghajanian, G. K., Gendelman, D. S.: Effects of clonidine on habituation and sensitization of acoustic startle in normal, decerebrate and locus coeruleus lesioned rats. Psychopharmacology 51, 243–253 (1977)
Davis, M., Gendelman, P. M., Gendelman, D. S.: 5-methoxy-N, N-dimethyltryptamine: Excitatory effects on acoustic startle in normal and acutely decerebrate rats. Submitted for publication, 1979
Davis, M., Wagner, A. R.: Startle responsivness following habituation to different intensities of tone. Psychon. Sci. 12, 337–338 (1968)
File, S. E., Deakin, J. F. W., Longden, A., Crow, T. J.: An investigation of the role of the locus coeruleus in anxiety and agonistic behavior. Brain Res., in press (1979)
Gallager, D. W.: Benzodiazepines: Potentiation of a GABA inhibitory response in the dorsal raphe nucleus. Eur. J. Pharmacol. 49, 133–144 (1978)
Geller, I., Beckman, E., Seifter, J.: Effects of reserpine and morphine on behavior suppressed by punishment. Life Sci. 2, 226 (1963)
Gold, M. S., Redmond, D. E., Jr., Kleber, H.: Clonidine in opiate withdrawal. Lancet I, 929–930 (1978)
Goldenberg, M., Snyder, C. H., Aranow, H., Jr.: New test for hypertension due to circulating epinephrine. JAMA 135, 971–976 (1947)
Greenblatt, D. J., Shader, R. I.: Pharmacotherapy of anxiety with benzodiazepines and beta-adrenergic blockers. In: Psychopharmacology: A generation of progress, M. A. Lipton, A. DiMascio, K. F. Killam, eds., pp. 1381–1390. New York: Raven 1978
Holmberg, G., Gershon, S.: Autonomic and psychic effects of yohimbine hydrochloride Pychopharmacologia (Berl.) 2, 93–106 (1961)
Huang, Y. H., Maas, J. W., Redmond, D. E., Jr.: Evidence for noradrenergic specificity of behavioral effects of electrical stimulation of the nucleus locus coeruleus. Neurosci. Abstr. 3, 251 (1977)
Huang, Y. H., Redmond, D. E., Jr., Snyder, D. R.: Loss of fear following bilateral lesions of the locus coeruleus in the monkey. Neurosci. Abstr. 2, 573 (1976)
Kapur, H., Mottram, D. R.: A comparative study on the pre- and post-synaptic alpha blocking activity of a series of benzodioxanes. Biochem. Pharmacol. 27, 1897–1880 (1978)
Kielholz, P. Beta-blockers and the central nervous system. Baltimore: University Park Press 1977
Korf, J, Bunney, B. S., Aghajanian, G. K.: Noradrenergic neurons: Morphine inhibition of spontaneous activity. Eur. J. Pharmacol. 25, 165–169 (1974)
Langer, S. Z.: Presynaptic regulation of catecholamine release. Biochem. Pharmacol. 23, 1793–1800 (1974)
Maas, J. W., Hattox, S. E., Landis, D. H.: The determination of a brain arteriovenous difference for 3-methoxy-4-hydroxyphenethylene glycol (MHPG). Brain Res. 118, 167–173 (1976)
Mottram, D. R., Kapur, H.: The α-adrenoceptor blocking effects of a new benzodioxane. J. Pharm. Pharmacol. 27, 295–296 (1975)
Pert, C. B., Kuhar, M. J., Snyder, S. H.: Autoradiographic localization of the opiate receptor in rat brain. Life Sci. 16, 1849–1854
Redmond, D. E., Jr.: Alteration in the function of the nucleus locus coeruleus: A possible model for studies on anxiety. In: Animal models in psychiatry and neurology, I. Hanin, E. Usdin, eds. pp. 293–304. Oxford: Pergamon 1977
Redmond, D. E., Jr.: New and old evidence for the involvement of a brain norepinephrine system in anxiety. In: The phenomenology and treatment of anxiety, W. E. Fann, ed. New York: Spectrum, in press, 1979
Redmond, D. E., Jr., Huang, Y. H., Snyder, D. R.: Behavioral changes following lesions of the locus coeruleus in Macaca arctoides. Neurosci. Abstr. 1, 472 (1976)
Redmond, D. E., Jr., Huang, Y. H., Snyder, D. R., Maas, J. W. Behavioral effects of stimulation of the locus coeruleus in the stumptail monkey (Macaca arctoides). Brain Res. 116, 502–510 (1976)
Simon, E. J.: Opiate receptor binding with 3H-etorphine. Neurosci. Res. Program Bull. 1975
Soffer, A.: Regitine and benodaine in the diagnosis of pheochromocytoma. Med. Clin. North Amer. 38, 375–384 (1954)
Starke, K., Endo, T., Taube, H. D.: Relative pre- and post-synaptic potencies of α-adrenoceptor agonists in the rabbit pulmonary artery. Naunyn Schmiedebergs Arch. Pharmacol. 291, 55–78 (1975)
Svensson, T. H., Bunney, B. S., Aghajanian, G. K.: Inhibition of both noradrenergic and serotonergic neurons in brain by the alpha-adrenergic agonist clonidine. Brain Res. 92, 291–306 (1975)
Svensson, T. H., Usdin, T.: Feedback inhibition of brain noradrenaline neurons by tricyclics: α-Receptor mediation. Science 202, 1089–1091 (1978)
Winer, B. J.: Statistical principles in experimental design. New. York: McGraw-Hill 1962
Young, W. S., III, Bird, S. J., Kuhar, M. J.: Iontophoresis of methionine-enkephalin in the locus coeruleus area. Brain Res. 129, 366–370 (1977)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Davis, M., Redmond, D.E. & Baraban, J.M. Noradrenergic agonists and antagonists: Effects on conditioned fear as measured by the potentiated startle paradigm. Psychopharmacology 65, 111–118 (1979). https://doi.org/10.1007/BF00433036
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00433036