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Effects of repeated administration of low doses of apomorphine in three behavioural models in the rat

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Journal of Neural Transmission - Parkinson's Disease and Dementia Section

Summary

A low dose of the dopamine (DA) receptor agonist apomorphine (APO 0.05 mg/kg) was given repetitively and the effects were tested in three different behavioural models: reduction of spontaneous locomotion, induction of yawning and decrease in water intake in water-deprived animals. The APO-induced suppression of exploration and decrease in water intake were not affected by a previous injection of APO given 1 or 3 hours before the test dose of APO. There was a small, but significant, decrease in the induction of yawning by a previous dose of APO given 1 hour or 30 min before the test dose. However, pretreatment with APO 3 hours before the test dose did not diminish the yawning response. It is suggested that the dopaminergic mechanisms mediating APO induced yawning are different from those mediating decrease in water intake and suppression of exploration. The results are also discussed in relation to the proposed efficiency of low doses of DA agonists in the treatment of various neurological and psychiatric disorders.

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References

  • Aghajanian GK, Bunney BS (1973) Central dopaminergic neurons: neurophysiological identification and responses to drugs. In: Snyder S, Usdin E (eds) Frontiers in catecholamine research. Pergamon Press, New York, pp 643–648

    Google Scholar 

  • Arbilla S, Nowak JZ, Langer SZ (1985) Rapid desensitization of presynaptic dopamine autoreceptors during exposure to exogenous dopamine. Brain Res 337: 11–17

    Google Scholar 

  • Baldessarini RJ (1980) Drug and the treatment of psychiatric disorders. In: Goodman Gillman A, Goodman LS, Gillman A (eds) The pharmacological basis of therapeutics. MacMillan, New York, pp 391–425

    Google Scholar 

  • Barzaghi F, Gropetti A, Montegazza P, Muller EE (1973) Reduction of food intake by apomorphine: a pimozide-sensitive effect. J Pharm Pharmacol 25: 909–911

    Google Scholar 

  • Baudray 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 

  • Bradbury AJ, Costall B, Lim SK, Naylor RJ (1982) Reduction in spontaneous locomotor activity by purported dopamine agonists: an analysis of the site and mechanism of action. In: Kohsaka M, Shohmori T, Tsukuda Y, Woodruff GN (eds) Advances in dopamine research. Oxford, Pergamon Press, pp 413–424

    Google Scholar 

  • Brown F, Campbell W, Mitchell PJ, Randall K (1985) Dopamine autoreceptors and the effects of drugs on locomotion and dopamine synthesis. Br J Pharmacol 84: 853–860

    Google Scholar 

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

    Google Scholar 

  • Carroll JB, Curtis GC, Kokman E (1977) Paradoxical response to dopamine agonists in tardive dyskinesia. Am J Psychiatry 134: 785–789

    Google Scholar 

  • Corsini GU, DelZompo M, Manconi S, Piccardi MP, Onali PL, Mangoni A, Gessa GL (1977) Evidence for dopamine receptors in the human brain mediating sedation and sleep. Life Sci 20: 1613–1618

    Google Scholar 

  • Costall B, Lim SK, Naylor RJ (1981) Characterisation of the mechanisms by which purported dopamine agonists reduce spontaneous locomotor activity of mice. Eur J Pharmacol 73: 175–188

    Google Scholar 

  • Dourish CT, Cooper SJ (1985) Behavioural evidence for the existence of dopamine autoreceptors: TIPS January: 17–18

  • Dourish CT, Cooper SJ, Phillips SR (1985) Yawning elicited by systemic and intrastriatal injection of pirebedil and apomorphine in the rat. Psychopharmacology 86: 175–181

    Google Scholar 

  • Farnebo L-O, Hamberger B (1971) Drug induced changes in the release of3H-monoamines from field-stimulated rat brain slices. Acta Physiol Scand [Suppl] 371: 35–44

    Google Scholar 

  • Gower AJ, Berendsen HHG, Princen MM, Broekkamp CLE (1984) The yawning-penile erection syndrome as a model for putative dopamine autoreceptor activity. Eur J Pharmacol 103: 81–89

    Google Scholar 

  • Hollister LE, Davies KL, Berger PA (1980) Apomorphine in schizophrenia. Commun Psychopharmacol 4: 277–281

    Google Scholar 

  • Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277: 93–96

    Google Scholar 

  • Ljungberg T (1987) Blockade by neuroleptics of water intake and operant responding for water in the rat: Anhedonia, motor deficit or both? Pharmacol Biochem Behav 27: 341–350

    Google Scholar 

  • Ljungberg T (1989) Dopamine D-2 antagonists reverses apomorphine induced decreased water intake in the rat: prediction of antipsychotic drugs with low incidence of extra-pyramidal side-effects. J Neural Transm 76: 79–90

    Google Scholar 

  • Ljungberg T, Ungerstedt U (1976) Automatic registration of behaviour related to dopamine and noradrenaline transmission. Eur J Pharmacol 36: 181–188

    Google Scholar 

  • Ljungberg T, Ungerstedt U (1978) A method for simultaneous recording of eight behavioural parameters related to monoamine neurotransmission. Pharmacol Biochem Behav 8: 483–489

    Google Scholar 

  • Martin EG, Bendensky RJ (1984) Mouse locomotor activity: an in vivo test for dopamine autoreceptor activation. J Pharmacol Exp Ther 229: 706–711

    Google Scholar 

  • Martres MP, Costentin J, Baudray M, Marcais H, Protais P, Schwartz JC (1977) Long term changes in the sensitivity of pre- and postsynaptic dopamine receptors in mouse striatum evidenced by behavioural and biochemical studies. Brain Res 136: 319–337

    Google Scholar 

  • Misslin R, Ropartz P, Jung L (1984) Impairment of responses to novelty by apomorphine and its antagonism by neuroleptics in mice. Psychopharmacology 82: 113–117

    Google Scholar 

  • Mogilnicka E, Klimek V (1977) Drugs affecting dopamine neurons and yawning behaviour. Pharmacol Biochem Behav 7: 303–305

    Google Scholar 

  • Mogilnicka E, Boissard CG, Delini-Stula A (1984) Effects of apomorphine, TL-99 and 3-PPP on yawning in rats. Neuropharmacology 23: 19–22

    Google Scholar 

  • Morelli M, Lagnoni R, Spina L, DiChiara G (1986) Antagonism of apomorphine induced yawning by SCH 23390: evidence against the dopamine autoreceptor hypothesis. Psychopharmacology 89: 259–260

    Google Scholar 

  • Protais P, Dubuc I, Costentin J (1983) Pharmacological characteristics of dopamine receptors involved in the dual effect of dopamine agonists on yawning behaviour in rats. Eur J Pharmacol 94: 271–280

    Google Scholar 

  • Puech AJ, Simon P, Chermat R, Boissier JR (1974) Profil neuropsychopharmacologique de l'apomorphine. J Pharmacol 5: 241–254

    Google Scholar 

  • Scheel-Krüger J (1986) The syndrome of sedation and yawning behaviour in the rat is dependent on postsynaptic dopamine D-2 receptors. Psychopharmacology 89: S32

    Google Scholar 

  • Serra G, Collu M, Gessa GL (1986) Dopamine receptors mediating yawning: are they autoreceptors. Eur J Pharmacol 120: 187–192

    Google Scholar 

  • Skirboll LR, Grace AA, Bunney BS (1979) Dopamine auto- and postsynaptic receptors: electrophysiological evidence for differential sensitivity to dopamine agonists. Science 206: 80–82

    Google Scholar 

  • Smith RC, Tamminga C, Davies JM (1977) Effect of apomorphine on schizophrenic symptoms. J Neural Transm 40: 171–176

    Google Scholar 

  • Starke K, Reimann A, Zumstein A, Hertting G (1978) Effects of dopamine receptor agonists and antagonists on release of dopamine in rabbit caudate nucleus in vitro. Naunyn Schmiedebergs Arch Pharmacol 305: 27–36

    Google Scholar 

  • Strömbom U (1976) Catecholamine receptor agonists: effects on motor activity and tyrosine hydroxylation in mouse brain. Naunyn Schmiedebergs Arch Pharmacol 292: 167–176

    Google Scholar 

  • Ståhle L (1987) Pharmacological studies on behavioural changes induced by dopamine agonists in the rat: a multivariate approach. Thesis, Department of Pharmacology, Karolinska Institute, Stockholm, Sweden

    Google Scholar 

  • Ståhle L, Ungerstedt U (1984) Assessment of dopamine autoreceptor agonists properties of apomorphine, (+)-3-PPP and (−)-3-PPP by recording of yawning behaviour in rats. Eur J Pharmacol 98: 307–310

    Google Scholar 

  • Ståhle L, Ungerstedt U (1986a) Different behavioural patterns induced by the dopamine agonist apomorphine analysed by multivariate statistics. Pharmacol Biochem Behav 24: 291–298

    Google Scholar 

  • Ståhle L, Ungerstedt U (1986b) Effects of neuroleptic drugs on the inhibition of exploratory behaviour induced by a low dose of apomorphine: implications for the identity of dopamine receptors. Pharmacol Biochem Behav 25: 473–480

    Google Scholar 

  • Ståhle L, Ungerstedt U (1987) Reduction of extracellular dopamine levels can be dissociated from suppression of exploratory behaviour in rats. Acta Physiol Scand 130: 533–534

    Google Scholar 

  • Ståhle L, Wold S (1986) On the use of multivariate statistical methods in pharmacological research. J Pharmacol Methods 20: 91–110

    Google Scholar 

  • Ståhle L, Wold S (1987) Partial least squares analysis with cross-validation for the two-class problem: a Monte-Carlo study. J Chemometrics 1: 185–196

    Google Scholar 

  • Tamminga CA, Gotts MD, Thaker GK, Alphs LD, Foster NL (1986) Dopamine agonist treatment of schizophrenia with N-propylnorapomorphine. Arch Gen Psychiatry 43: 398–402

    Google Scholar 

  • Tolosa ES, Sparber SB (1974) Apomorphine in Huntingtons chorea: clinical observations and theoretical considerations. Life Sci 15: 1371–1380

    Google Scholar 

  • Ungerstedt U, Herrera-Marschitz M, Jungnelius U, Ståhle L, Tossman U, Zetterström T (1982) Dopamine synaptic mechanisms reflected in studies combining behavioural recording and brain dialysis. In: Kohsaka M, Shohmori T, Tsukuda Y, Woodruff GN (eds) Advances in dopamine research. Oxford, Pergamon Press, pp 219–231

    Google Scholar 

  • Walters JR, Roth RH (1976) Dopaminergic neurons: an in vivo system for measuring drug interactions with presynaptic receptors. Naunyn Schmiedebergs Arch Pharmacol 296: 5–14

    Google Scholar 

  • Wang RY (1981) Dopaminergic neurons in the rat ventral tegmental area. I. Identification and characterization. Brain Res Rev 3: 123–140

    Google Scholar 

  • Westfall TC, Besson MJ, Giorguieff MF, Glowinski J (1976) The role of presynaptic receptors in the release and synthesis of3H-dopamine by slices of rat striatum. Naunyn Schmiedebergs Arch Pharmacol 292: 279–287

    Google Scholar 

  • Willner P, Towell A, Muscat R (1985) Apomorphine anorexia: a behavioural and neuropharmacological analysis. Psychopharmacology 87: 351–356

    Google Scholar 

  • Wold H (1982) Soft modelling: the basic design and some extentions. In: Jöreskog KG, Wold H (eds) Systems under indirect observation, vol. 2. North Holland, Amsterdam, pp 1–54

    Google Scholar 

  • Wold S, Albano C, Dunn III WJ, Esbensen K, Hellberg S, Johansson E, Sjöström M (1983) Pattern recognition: finding and using regularities in multivariate data. In: Martens H, Russworm Jr H (eds) Food research and data analysis. Applied Science Publishers, London, pp 1–36

    Google Scholar 

  • Yamada K, Furukawa T (1980) Direct evidence for involvement of dopaminergic inhibition and cholinergic activation in yawning. Psychopharmacology 67: 39–43

    Google Scholar 

  • Zetterström T, Ungerstedt U (1984) Effects of apomorphine on the in vivo release of dopamine and its metabolites, studied by brain dialysis. Eur J Pharmacol 97: 29–36

    Google Scholar 

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Author notes

  1. T. Ljungberg

    Present address: Institut de Physiologie, Université de Fribourg, Rue du Musée 5, CH-1700, Fribourg, Switzerland

Authors and Affiliations

  1. Department of Pharmacology, Karolinska Institute, P.O.Box 60 400, S-10401, Stockholm, Sweden

    T. Ljungberg, L. Ståhle & U. Ungerstedt

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  1. T. Ljungberg
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  2. L. Ståhle
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  3. U. Ungerstedt
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Ljungberg, T., Ståhle, L. & Ungerstedt, U. Effects of repeated administration of low doses of apomorphine in three behavioural models in the rat. J Neural Transm Gen Sect 1, 165–175 (1989). https://doi.org/10.1007/BF02248666

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  • DOI: https://doi.org/10.1007/BF02248666

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