Abstract
Ten behavioural variables were recorded by means of an automatic holeboard apparatus. The behaviour of rats placed for the first time in the apparatus was recorded for 10 min. The suppression of this exploratory behaviour by the dopamine agonist apomorphine (0.01–0.1 mg/kg) was shown to bereversible in a surmountable fashion by the dopamine antagonist sulpiride (2 and 4 mg/kg). Suppression of exploration induced by clonidine (0.05 0.2 mg/kg) or diazepam (2 mg/kg) was not antagonised by sulpiride (10 and 50 mg/kg, respectively). The partial dopamine D1-agonist SKF 38393 (2–20 mg/kg) also suppressed exploration but neither sulpiride (20 mg/kg) nor the D1-antagonist SCH 23390 (0.02 mg/kg) could antagonise this effect. The data show that dopamine agonist induced suppression of exploration display pharmacological characteristics of a receptor-mediated response and the data support our previous suggestion that these receptors may be pharmacologically distinct from other dopamine D2-receptors.
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References
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. Pergamon Press, Oxford, pp 413–424
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
Carroll JB, Curtis GC, Kokman E (1977) Paradoxical response to dopamine agonists in tardive dyskinesia. Am J Psychiatry 134:785–789
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
Corsini GU, DelZompo M, Melis GB, Magnoni A, Gessa GL (1979) (-)-sulpiride as a specific antagonist of “low dose” effects of apormorphine in man. In: Spano PF, Trabucchi M, Corsini GU, Gessa GL (eds) Sulpiride and other benzamides. Italian Brain Research Foundation Press, Milan, pp 255–267
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
Cutler NR, Jeste DV, Kaufman CA, Karoum F, Schran HF, Wyatt RJ (1984) Low dose bromocriptine: a study of acute effects in chronic medicated schizophrenics. Prog Neuropsychopharmacol Biol Psychiatry 8:277–283
DiChiara G, Porceddu ML, Vargiu L, Argiolas A, Gessa GL (1976) Evidence for dopamine receptors mediating sedation in the mouse brain. Nature 264:564–565
Hjorth S (1983) On the mode of action of 3-(3-hydroxyphenyl)-N-n-propylpierazine, 3-PPP, and its enantiomers. Acta Physiol Scand [Suppl] 517:1–58 (Thesis, Department of Pharmacology, University Göteborg, Sweden)
Hyttel J (1983) SCH 23390-the first selective dopamine D1-antagonist. Eur J Pharmacol 91:153–154
Iorio LC, Barnett A, Leitz FH, Houser VP, Korduba CA (1983) SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems. J Pharmacol Exp Ther 226:462–468
Jenner P, Marsden CD (1981) Substituted benzamide drugs as selective neuroleptic agents. Neuropharmacology 20:1285–1293
Ljungberg T, Ungerstedt U (1976) Automatic registration of behaviour related to dopamine and noradrenaline transmission. Eur J Pharmacol 36:181–188
Ljungberg T, Ungerstedt U (1978) A method for simultaneous recording of eight behavioural parameters related to monoamine neurotransmission. Pharmacol Biochem Behav 8:483–489
Ljungberg T, Lidfors L, Enquist M, Ungerstedt U (1987) Impairment of decision making in rats by diazepam: implications for the “anticonflict” effects of benzodiazepines. Psychopharmacology 92:416–423
Martin EG, Bendensky RJ (1984) Mouse locomotor activity: an in vivo test for dopamine autoreceptor activation. J Pharmacol Exp Ther 229:706–711
Meltzer HY, Kolakowska T, Robertson A, Tricou BJ (1983) Effect of low-dose bromocriptine in treatment of psychosis: the dopamine autoreceptor stimulation strategy. Psychopharmacology 81:37–41
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
Molloy AG, Waddington JL (1985) Sniffing, rearing and locomotor responses to the D-1 dopamine receptor agonist R-SK & F 38393 and to apomorphine: different interactions with the selective D-1 and D-2 antagonists SCH 23390 and metoclopramide. Eur J Pharmacol 108:305–308
Ögren S-O, Rodebjer A, Ängeby K (1984) The “presynaptic” blocking potency of sulpiride and haloperidol in the rat is agedependent. Neurosci Lett 46:203–207
Puesch AJ, Simon P, Chermat R, Boissier JR (1974) Profil neuropsychopharmacologique de l'apomorphine. J Pharmacol 5:241–254
Schildt HO (1949) pAx and competitive drug antagonism. Br J Pharmacol 4:277–280
Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32:229–313
Setler PE, Sarau HM, Cirkle CL, Saunders HL (1978) The central effects of a novel dopamine agonist. Eur J Pharmacol 50:419–430
Smith RC, Tamminga C, Davies JM (1977) Effect of apomorphine on schizophrenic symptoms. J Neural Transm 40:171–176
Ståhle L (1987) Pharmacological studies on behavioural changes induced by dopamine agonists in the rat: a multivariate approach. Thesis, Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden
Ståhle L, Ungerstedt U (1986a) Different behavioural patterns induced by the dopamine agonist apomorphine analysed by multivariate statistics. Pharmacol Biochem Behav 24:291–298
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
Ståhle L, Ungerstedt U (1986) On the mode of action of six putative dopamine receptor agonists on suppression of exploratory behaviour in the rat. Psychopharmacology 91:139–146
Ståhle L, Wold S (1986) On the use of some multivariate statistical methods in pharmacological research. J Pharmacol Methods 16:91–110
Ståhle L, Wold S (1987) Partial least squares analysis with crossvalidation for the two-class problem: a Monte Carlo study. J Chemometrics 1:185–196
Ståhle L, Wold S (1988) Multivariate data analysis and experimental design inbiomedical research. Prog Med Chem 26:300–349
Starke K, Späth L, Lang JD, Adelung C (1983) Further functional in vitro comparison of pre-and postsynaptic dopamine receptors in rabbit caudate nucleus. Naunyn Schmiedebergs Arch Pharmacol 323:298–306
Strömbom U (1976) Catecholamine receptor agonists: effects on motor activity and tyrosine hydroxylation in mouse brain. Naunyn Schmiedebergs Arch Pharmacol 292:167–176
Sumners C, De Vries JB, Horn AS (1981) Behavioural and neurochemical studies on apomorphine-induced hypomotility in mice. Neuropharmacology 20:1203–1208
Tolosa ES, Sparber SB (1974) Apomorphine in Huntington's chorea: clinical observations and theoretical consideration. Life Sci 15:1371–1380
Wold H (1982) Soft modeling, the basic design and some extentions. In: Jöreskog KG, Wold H (eds) Systems under indirect observation, vol II, pp 1–54
Wold S, Ruhe A, Wold H, Dunn III WJ (1984) The collinearity problem in linear regression, the partial least squares (PLS) approach to generalized inverses. SIAM J Sat Comput 5:735–743
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Ståhle, L., Ungerstedt, U. On the selectivity and specificity of the antagonism of apomorphine-induced suppression of exploration by sulpiride. Psychopharmacology 99, 75–79 (1989). https://doi.org/10.1007/BF00634456
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DOI: https://doi.org/10.1007/BF00634456