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The comparative long-term effects of ciladopa (AY-27,110), a chemically novel dopaminergic agonist, in 6-OHDA-lesioned and intact rats

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Abstract

The effect of the chemically novel dopaminergic agonist, ciladopa (AY-27,110) was studied on rotational behavior in unilaterally 6-OHDA-lesioned rats and on stereotyped behavior in normal animals during and after chronic treatment. Ciladopa, at a 1.25 mg/kg SC daily dose, was administered for 4 and 6 weeks to the lesioned and normal animals, respectively. This dose was threshold for turning but subthreshold with respect to stereotypy. Both behaviors were evaluated weekly during chronic treatment and biweckly for 11 weeks after its discontinuation in response to doses previously shown to elicit turning and stereotypy. The chronic administration of ciladopa enhanced rotational behavior considerably more and with an earlier onset than stereotypy, although the duration of behavioral supersensitivity after cessation of treatment was the same. These results indicate that behaviors mediated by supersensitive or intact dopamine receptors are differently affected by chronic dopamine agonist treatment. The results are discussed in relation to their potential therapeutic implications and current concepts of agonist-induced supersensitivity.

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References

  • Agnati LF, Fuxe K, Calza L, Zini I, Benefenati F, Farabegoli C, Goldstein M (1983) Chronic treatment with L-dopa plus carbidopa in hemi-transected rats: Preferential effects at intact dopamine synapses leading to behavioural signs of dopamine receptor supersensitivity. Acta physiol Scand 118:27–34

    Google Scholar 

  • Bailey RC, Jackson DM (1978) A pharmacological study of changes in central nervous system receptor responsiveness after long-term dexamphetamine and apomorphine administration. Psychopharmacology 56:317–326

    Google Scholar 

  • Bailey R, Crisp E, Jackson DM, Jenkins O (1981) Chronic L-dopa treatment of mice: A behavioral and biochemical study. J Neural Transm 50:209–224

    Google Scholar 

  • Baudry M, Costentin J, Marcais H, Martres MP, Protais P, Schwartz JC (1977) Decreased responsiveness to low doses of apomorphine after dopamine agonists and the possible involvement of hyposensitivity of dopamine ‘autoreceptors’. Neurosci Lett 4:203–207

    Google Scholar 

  • Carlsson A (1975) Receptor-mediated control of dopamine metabolism. In: Usdin E, Bunney WE Jr (eds) Pre- and postsynaptic receptors. Marcel Dekker, New York, pp 49–63

    Google Scholar 

  • Costall B, Naylor FJ (1973) On the mode of action of apomorphine. Eur J Pharmacol 21:350–361

    Google Scholar 

  • Cotzias GC, Papavasiliou PS, Steck A, Duby S (1971) Parkinsonism and levodopa. Clin Pharmacol Ther 12:319–322

    Google Scholar 

  • Fuxe K, Ogren SO, Agnati LF, Andersson K, Hall H, Köhler C, Fredholm B (1980) Central monoamine synapses as sites of action for ergot drugs. In: Goldstein M, Lieberman A, Calne DB, Thorner MO (eds) Ergot compounds and brain function: Neuroendocrine and neuropsychiatric aspects. Raven, New York, pp 41–62

    Google Scholar 

  • Globus M, Bannet J, Lerer B, Belmaker RH (1982) The effect of chronic bromocriptine and L-dopa on spiperone binding and apomorphine-induced stereotypy. Psychopharmacology 78:81–84

    Google Scholar 

  • Grimes JD (1984) Bromocriptine in Parkinson's disease: Results obtained with high and low dose therapy. Can J Neurol Sci (Suppl) 11:225–228

    Google Scholar 

  • De Groot J (1959) The rat forebrain in stereotaxic coordinates. Verh K Ned Akad Wetenschap Natuurk 52:1

    Google Scholar 

  • Klawans HL, Goetz C, Nausieda PA, Weiner WJ (1977) Levodopa-induced dopamine receptor hypersensitivity. Ann Neurol 2:125–129

    Google Scholar 

  • Koller WC, Weiner WJ, Diamond BI, Nausieda PA, Klawans HL (1980) The pharmacological evaluation of pergolide mesylate as a potential anti-Parkinson agent. Neuropharmacology 19:831–837

    Google Scholar 

  • Lieberman AN, Leibowitz M, Neophytides A, Kupersmith M, Mehl S, Kleinberg D, Serby M, Goldstein M (1979) Pergolide and lisuride for Parkinson's disease. Lancet 2:1129–1130

    Google Scholar 

  • Marsden CD, Parkes JD (1977) Success and problems of long-term levodopa therapy in Parkinson's disease. Lancet 1:345–349

    Google Scholar 

  • Muller P, Seeman P (1979) Presynaptic subsensitivity as a possible basis for sensitization by long-term dopamine mimetics. Eur J Pharmacol 55:149–157

    Google Scholar 

  • Nausieda PA, Weiner WJ, Kanapa DJ, Klawans HL (1978) Bromocriptine-induced behavioral hypersensitivity: Implications for the therapy of Parkinsonism. Neurology 28:1183–1188

    Google Scholar 

  • Parkes D (1977) Bromocriptine. Adv Drug Res 12:247–344

    Google Scholar 

  • Pinder RM, Brogden RN, Sawyer PR, Speight TM, Avery GS (1976) Levodopa and decarboxylase inhibitors: A review. Drugs 11:331–377

    Google Scholar 

  • Porreca F, Cowan A, Tallarida RJ (1982) Differentiation of apomorphine from bromocriptine, piribidel and TRH by chronic administration in rats. Psychopharmacology 76:70–74

    Google Scholar 

  • Pycock CJ, Marsden CD (1977) Central dopaminergic receptor supersensitivity and its relevance to Parkinson's disease. J Neurol Sci 31:113–121

    Google Scholar 

  • Pycock CJ, Marsden CD (1978) The rotating rodent: A two component system? Eur J Pharmacol 47:167–175

    Google Scholar 

  • Pycock CJ, Dawbarn D, O'Shaughnessy C (1982) Behavioural and biochemical changes following chronic administration of L-dopa to rats. Eur J Pharmacol 79:201–215

    Google Scholar 

  • Riffee WH, Wilcox RE, Vaughn DM, Smith RV (1982) Dopamine receptor sensitivity after chronic dopamine agonists. Striatal 3H-spiroperidol binding in mice after chronic administration of high doses of apomorphine, N-n-propylnorapomorphine and dextroamphetamine. Psychopharmacology 77:146–149

    Google Scholar 

  • Scheffe H (1970a) The two-way layout with one observation per cell. In: The analysis of variance. John Wiley & Sons, New York, pp 98–106

    Google Scholar 

  • Scheffe H (1970b) T-method of multiple comparison. In: The analysis of variance. John Wiley & Sons, New York, pp 73–75

    Google Scholar 

  • Siegel S (1956a) Kruskal-Wallis test. In: Nonparametric statistics for the behavioral sciences. McGraw-Hill, New York, pp 184–193

    Google Scholar 

  • Siegel S (1956b) Mann-Whitney U test. In: Nonparametric statistics for the behavioral sciences. McGraw-Hill, New York, pp 116–127

    Google Scholar 

  • Smith RC, Strong JR, Hicks PB, Samorajski T (1979) Behavioral evidence for supersensitivity after chronic bromocriptine administration. Psychopharmacology 60:241–246

    Google Scholar 

  • Teychenne PF, Bergsrud D, Racy A, Elton RL, Vern B (1982) Bromocriptine: Low-dose therapy in Parkinson disease. Neurology 32:577–583

    Google Scholar 

  • Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl 367:69–93

    Google Scholar 

  • Voith K (1982) The behavioral pharmacology of AY-27,110, a chemically novel dopaminergic agonist. 12th Annual Meeting Soc Neurosci Abstr 128.18, Minneapolis, MN

  • Voith K (1984) The behavioral pharmacology of AY-27,110, a novel nonergot dopaminergic agonist. Drug Dev Res 4:391–404

    Google Scholar 

  • Voith K, Cummings JR (1976) Behavioral studies on the enantiomers of butaclamol demonstrating absolute optical specificity for neuroleptic activity. Can J Physiol Pharmacol 54:551–560

    Google Scholar 

  • Wilcox RE, Riffee WH, Chen PC, Hammett S, Smith RV (1980) Behavioral facilitation following chronic administration of N-n-propylnorapomorphine. Psychopharmacology 72:113–115

    Google Scholar 

  • Wilner KD, Butler IJ, Seifert WE, Clement-Cormier YC (1980) Biochemical alterations of dopamine receptor responses following chronic L-dopa therapy. Biochem Pharmacol 29:701–706

    Google Scholar 

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Voith, K. The comparative long-term effects of ciladopa (AY-27,110), a chemically novel dopaminergic agonist, in 6-OHDA-lesioned and intact rats. Psychopharmacology 85, 405–409 (1985). https://doi.org/10.1007/BF00429654

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  • DOI: https://doi.org/10.1007/BF00429654

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