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Studies on the mechanism of clonidine-induced mydriasis in the rat

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Summary

  1. 1.

    Intravenous administration of clonidine hydrochloride (3–100μg/kg) produced a dose-dependent pupillary dilation in anaesthetized rats. All experiments were carried out in rats in which vagosympathetic nerve trunks were sectioned bilaterally at the cervical level.

  2. 2.

    Clonidine-induced mydriasis was present only in those preparations having intact parasympathetic neural tone to the iris.

  3. 3.

    Depletion of CNS monoamines by more than 95% with reserpine (5mg/kg) and alpha-methyl-para-tyrosine (2×300mg/kg) failed to alter the dose-response relation to clonidine.

  4. 4.

    Pretreatment with the alpha-2-adrenoceptor antagonist, yohimbine hydrochloride (1.5 mg/kg), produced about a 10-fold shift to the right in the pupillary dose-response curve to clonidine. Yohimbine administered after the highest dose of clonidine also antagonized the mydriatic response.

  5. 5.

    The above results suggest that clonidine acts on CNS post-synaptic alpha-2-adrenoceptors to produce mydriasis by withdrawal of parasympathetic neural tone to the iris.

  6. 6.

    In an attempt to assess the physiological substrate(s) involved, mydriatic responses, due to parasympatho-inhibition, were evoked by electrial stimulation of ascending (sciatic nerve and medullary) and descending (hypothalamic) pathways.

  7. 7.

    Yohimbine (0.3 and 1.0mg/kg) produced a dose-dependent inhibition of the pupillary dilation evoked by stimulation of the sciatic nerve and medullary loci, whereas these doses of yohimbine failed to alter the dilation in response to hypothalamic stimulation.

  8. 8.

    Similarly, monoamine depletion greatly antagonized the pupillary dilation elicited by sciatic nerve and medullary stimulation without significantly affecting mydriasis due to hypothalamic stimulation.

  9. 8.

    These results suggest that pupillary dilation produced by activation of ascending inhibitory mechanisms may utilize a monoamine as an inhibitory neurotransmitter (perhaps noradrenaline) and that inhibition descending from the hypothalamus is not monoaminergic. It is further speculated that clonidine may produce mydriasis in this species by activation of CNS post-synaptic alpha-2-adrenoceptors (perhaps on neurons of the Edinger-Westphal nucleus) which normally subserve tonic inhibition arising from the periphery.

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References

  • Baum T, Shropshire AT (1977) Susceptibility of spontaneous sympathetic outflow and sympathetic reflexes to depression by clonidine. Eur J Pharmacol 44:121–129

    Google Scholar 

  • Berridge TL, Gadie B, Roach AG, Tulloch (1983) α2-Adrenoceptor agonists induce mydriasis in the rat by an action within the central nervous system. Br J Pharmacol 78:507–515

    Google Scholar 

  • Bogdanski DF, Sulser F, Brodie BB (1961) Comparative action of reserpine, tetrabenazine and chlorpromazine on central parasympathetic activity: effects on pupillary size and lacrimation in rabbit and on salivation in dog. J Pharmacol Exp Therap 132:176–182

    Google Scholar 

  • Coote JH, Macleod VH (1974) The influence of bulbospinal monoaminergic pathways on sympathetic nerve activity. J Physiol (Lond) 241:453–475

    Google Scholar 

  • Coote JH, Macleod VH, Fleetwood-Walker S, Gilbey MP (1981) The response of individual sympathetic preganglionic neurones to microelectrophoretically applied endogenous monoamines. Brain Res 215:135–145

    Google Scholar 

  • Dahlström A, Fuxe K, Hillarp N-A, Malmfors T (1964) Adrenergic mechanisms in the pupillary light-reflex path. Acta Physiol Scand 62:119–124

    Google Scholar 

  • De Groat WC, Ryall RW (1967) An excitatory action of 5-hydroxytryptamine on sympathetic preganglionic neurones. Exp Brain Res 3:299–305

    Google Scholar 

  • Dembowsky K, Czachurski J, Amendt K, Seller H (1980) Tonic descending inhibition of the spinal somato-sympathetic reflex from the lower brain stem. J Auton Nerv Syst 2:157–182

    Google Scholar 

  • Franz DN, Madsen PW (1982) Differential sensitivity of four central sympathetic pathways to depression by clonidine. Eur J Pharmacol 78:53–59

    Google Scholar 

  • Gherezghiher T, Koss MC (1979) Clonidine mydriasis in the rat. Eur J Pharmacol 57:263–266

    Google Scholar 

  • Gherezghiher T, Christensen HD, Koss MC (1982) Studies on the mechanism of methyl-dopa-induced mydriasis in the cat. Naunyn-Schmiedeberg's Arch Pharmacol 320:58–62

    Google Scholar 

  • Gherezghiher T, Koss MC, Christensen HD (1983) Alpha-methyl-DOPA-induced mydriasis in the cat. Relationship between pupillary response and the oculomotor perfusate concentration of methyldopa and its metabolites. Naunyn-Schmiedeberg's Arch Pharmacol 324:201–206

    Google Scholar 

  • Guyenet PG, Cabot JB (1981) Inhibition of sympathetic preganglionic neurons by catecholamines and clonidine: mediation by an alpha-adrenergic receptor. J Neurosci 1:908–917

    Google Scholar 

  • Haeusler G (1974) Clonidine-induced inhibition of sympathetic activity: No indication for a central presynaptic or an indirect sympathomimetic mode of action. Naunyn-Schmiedeberg's Arch Pharmacol 286:97–111

    Google Scholar 

  • Hamel EG, Jr, Kaelber WW (1961) Reserpine action on the central nervous system of the cat. Am J Physiol 200:195–200

    Google Scholar 

  • Hodes R (1940) The efferent pathway for reflex pupillo-motor activity. Am J Physiol 131:144–155

    Google Scholar 

  • Koss MC (1979a) Clomdine mydriasis in the cat: further evidence for a CNS postsynaptic action. Naunyn-Schmiedeberg's Arch Pharmacol 309:235–239

    Google Scholar 

  • Koss MC (1979b) Topical clonidine produces mydriasis by a central nervous system action. Eur J Pharmacol 55:305–310

    Google Scholar 

  • Koss MC (1980a) Studies on the mechanism of amphetamine mydriasis in the cat. J Pharmacol Exp Therap 213:49–53

    Google Scholar 

  • Koss MC (1980b) Methyldopa produces central inhibition of parasympathetic activity in the cat. Naunyn-Schmiedeberg's Arch Pharmacol 314:135–139

    Google Scholar 

  • Koss MC (1981) Analysis of pupillary dilation produced by analogs of clonidine. Eur J Pharmacol 74:303–309

    Google Scholar 

  • Koss MC, Christensen HD (1979) Evidence for a central postsynaptic action of clonidine. Naunyn-Schmiedeberg's Arch Pharmacol 307:45–50

    Google Scholar 

  • Koss MC, San LC (1976) Analysis of clonidine-induced mydriasis. Invest Ophthal 15:566–570

    Google Scholar 

  • Koss MC, Gherezghiher T, Nomura N (1984) CNS adrenergic inhibition of parasympathetic oculomotor tone. J Auton Nerv Syst 10:55–68

    Google Scholar 

  • Parsons JH (1901) On dilatation of the pupil from stimulation of the cortex cerebri. J Physiol (Lond) 25:366–379

    Google Scholar 

  • Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain. 2. edn. Plenum Press, New York

    Google Scholar 

  • Sigg EB, Sigg TD (1967( Adrenergic modulation of central function. In: Garattini S, Dukes MNG (eds) Antidepressant drugs. Excerpta Med Foundation, pp 172–178

  • Sigg EB, Sigg TD (1973) The modification of the pupillary light reflex by chlorpromazine, diazepam and pentobarbital. Brain Res 50:77–86

    Google Scholar 

  • Ury B, Gellhorn E (1939) Role of the sympathetic system in reflex dilatation of pupil. J Neurophysiol 2:268–275

    Google Scholar 

  • Weinstein EA, Bender MB (1941) Pupillodilator reactions to sciatic and diencephalic stimulation: a comparative study in cat and monkey. J Neurophysiol 4:44–50

    Google Scholar 

  • Whishaw IQ, Cioe JDD, Previsich N, Kolb B (1977) The variability of the interaural line vs the stability of bregma in rat stereotaxic surgery. Physiol Behav 19:719–722

    Google Scholar 

  • Yonkman FF, Stilwell D, Jeremias R (1944) The adrenolytic and sympatholytic actions of yohimbine and ethyl yohimbine. J Pharmacol Exp Ther 81:111–115

    Google Scholar 

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Authors and Affiliations

  1. Departments of Pharmacology and Ophthalmology, University of Oklahoma health Sciences Center, P.O. Box 26901, 73190, Oklahoma City, OK, USA

    J. A. Hey, T. Gherezghiner & M. C. Koss

  2. Dean A. McGee Eye Institute, P.O. Box 26901, 73190, Oklahoma City, OK, USA

    J. A. Hey, T. Gherezghiner & M. C. Koss

Authors
  1. J. A. Hey
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  2. T. Gherezghiner
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  3. M. C. Koss
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Hey, J.A., Gherezghiner, T. & Koss, M.C. Studies on the mechanism of clonidine-induced mydriasis in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 328, 258–263 (1985). https://doi.org/10.1007/BF00515551

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  • DOI: https://doi.org/10.1007/BF00515551

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