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Effects of α2-adrenoceptor agonists on locus coeruleus firing rate and brain noradrenaline turnover in N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-treated rats

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Summary

Previous studies have shown that a low dose of the alkylating compound N-ethoxycarbonyl-2-ethoxy1,2-dihydroquinoline (EEDQ) reduces the density of α2-adrenoceptors in rat cerebral cortex and antagonizes the effects of an α2-adrenoceptor agonist on noradrenaline release in rat cortical slices. In the present study, a corresponding dose of EEDQ (1 mg/kg, s. c., 24 h) was shown to reduce the effect of the α2-adrenoceptor agonists clonidine and guanfacine on noradrenaline turnover in rat brain while not affecting the inhibitory effect of clonidine on locus coeruleus (LC) cell firing. When considerably higher doses of EEDQ were administered (10 and 20 mg/kg, s. c., 24 h) not only the biochemical but also the electrophysiological effects of clonidine were markedly reduced (or even reversed). The data support the notion that EEDQ decreases the responsiveness of brain α2-adrenergic receptors; moreover, they indicate that α2-adrenoceptors regulating LC activity are characterized by a larger receptor reserve or are less sensitive to the influence of alkylation than are the population of α2-adrenoceptors regulating noradrenaline utilization.

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References

  • Adler CH, Meller, E, Goldstein M (1985) Recovery of α2-adrenoceptor binding and function after irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Eur J Pharmacol 116:175–178

    Google Scholar 

  • Adler CH, Meller E, Goldstein M (1987) Receptor reserve at the α2-adrenergic receptor in the rat cerebral cortex. J Pharmacol Exp Ther 240:508–515

    Google Scholar 

  • Andén N-E, Grabowska M, Strömbom U (1976) Different α2-adrenoceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn-Schmiedeberg's Arch Pharmacol 292:43–52

    Google Scholar 

  • Bylund DB (1988) Subtypes of α2-adrenoceptors: pharmacological and molecular evidence converge. Trends Pharmacol Sci 9:356–361

    Google Scholar 

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

    Google Scholar 

  • Crocker AD, Cameron DL (1989) Receptor alkylating agents: Novel tools for the study of receptor function in the central nervous system of the rat. Clin Exp Pharmacol Physiol 16:545–548

    Google Scholar 

  • Curet E, Dennis T, Scatton B (1987) Evidence for the involvement of presynaptic α2-adrenoceptors in the regulation of norepinephrine metabolism in rat brain. J Pharmacol Exp Ther 240:327–336

    Google Scholar 

  • Ekman A, Eriksson E (1991) Pituitary and brain D2 receptor density measured in vitro and in vivo in EEDQ treated male rats. Life Sci 48:321–331

    Google Scholar 

  • Engberg, G, Elam M, Svensson TH (1982) Clonidine withdrawal: activation of brain noradrenergic neurons with specifically reduced α2-receptor sensitivity. Life Sci 30:235–243

    Google Scholar 

  • Ennis M, Aston-Jones G (1986) A potent excitatory input to the nucleus locus coeruleus from the ventrolateral medulla. Brain Res 374:299–305

    Google Scholar 

  • Farnebo L-O, Hamberger B (1971) Drug induced changes in the release of [3H]-noradrenaline from field stimulated rats iris. Br J Pharmacol 43:97–106

    Google Scholar 

  • Felice LJ, Felice JD, Kissinger PT (1978) Determination of catecholamines in rat brain parts by reversed-phase ion-pair liquid chromatography. J Neurochem 31:1461–1465

    Google Scholar 

  • Freedman JE, Aghajanian GK (1984) Idazoxan (RX 781094) selectively antagonizes α2-adrenoceptors on the rat neurons. Eur J Pharmacol 105:265–272

    Google Scholar 

  • König JFR, Klippel RA (1970) The rat brain: A stereotaxical atlas. Krieger, Huntington, New York

    Google Scholar 

  • Langer SZ (1977) Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol 60:481–497

    Google Scholar 

  • Marwaha J, Aghajanian GK (1982) Relative potencies of α1- and α2-antagonists in the locus coeruleus, dorsal raphe and dorsal geniculate nuclei: an electrophysiological study. J Pharmacol Exp Ther 222:287–293

    Google Scholar 

  • Meller E, Helmer-Matyjek E, Bohmaker K, Adler CH, Friedhoff AJ, Goldstein M (1986) Receptor reserve at striatal dopamine autoreceptors: implications for selectivity of dopamine agonists. Eur J Pharmacol 123:311–314

    Google Scholar 

  • Nasseri A, Minnemann KP (1987) Relationship between alpha2-adrenergic receptor binding sites and the functional receptors inhibiting norepinephrine release in rat cerebral cortex. Mol Pharmacol 32:655–662

    Google Scholar 

  • Nissbrandt H, Engberg G, Magnusson T, Wikström, H, Carlsson A (1988) NSD 1034 An amino acid decarboxylase inhibitor with a stimulatory action on dopamine synthesis not mediated by classical dopamine receptors. Naunyn-Schmiedeberg's Arch Pharmacol 338:148–161

    Google Scholar 

  • Pilc A, Vetulani J, Nomura S, Enna SJ (1989) An in vivo procedure for the selective inactivation of rat brain cerebral cortical α-adrenoceptors using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Brain Res 493:8–13

    Google Scholar 

  • Raiteri M, Maura G, Versace P (1983) Functional evidence for two stereochemically different alpha2-adrenoceptors regulating central norepinephrine and serotonin release. J Pharmacol Exp Ther 224:679–684

    Google Scholar 

  • Salzman PM, Roth RH (1979) Poststimulation catecholamine synthesis and tyrosine hydroxylase activation in central noradrenergic neurons. I. In vivo stimulation of the locus coeruleus. J Pharmacol Exp Ther 212:64–73

    Google Scholar 

  • Scholtysik G (1980) Pharmacology of guanfacine. Br J Clin Pharmacol 10 (Suppl 1):21S-24S

    Google Scholar 

  • Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77:1–124

    Google Scholar 

  • Svensson TH (1978) Central alpha-adrenoceptors and affective symptoms and disorder: In: Lindenlaub E, Garattini S (eds) Depressive disorders (13th Symp. Medical Hoechst, Rome). FK Schattauer Verlag, Stuttgart, New York, pp 245–254

    Google Scholar 

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

    Google Scholar 

  • Takeushi K, Kogure M, Hashimoto T (1987) Comparison of agonistic and antagonistic actions of guanabenz and guanfacin on α1- and α2-adrenoceptors in isolated smooth muscles. Jpn J Pharmacol 43:265–275

    Google Scholar 

  • U'Prichard DC, Bechtel WD, Rouot BM, Snyder SH (1979) Multiple apparent α-noradrenergic receptor binding sites in rat brain: Effect of 6-hydroxydopamine. Mol Pharmacol 16:47–60

    Google Scholar 

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  1. Department of Pharmacology, University of Göteborg, PO Box 33031, S-400 33, Göteborg, Sweden

    Göran Engberg & Elias Eriksson

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  1. Göran Engberg
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  2. Elias Eriksson
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Engberg, G., Eriksson, E. Effects of α2-adrenoceptor agonists on locus coeruleus firing rate and brain noradrenaline turnover in N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-treated rats. Naunyn-Schmiedeberg's Arch Pharmacol 343, 472–477 (1991). https://doi.org/10.1007/BF00169548

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  • DOI: https://doi.org/10.1007/BF00169548

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