We report on the pharmacological effects of the 20 fold D 3 vs. D 2 dopamine receptor preferring compound U 99194 A. It is shown that U 99194 A increases rat locomotor activity at doses that do not increase release or utilisation of dopamine in the striatum or the nucleus accumbens significantly. The data do not support any direct agonist action of U 99194 A at dopamine receptors. It is suggested that U 99194 A can antagonise a population of postsynaptic dopamine receptors involved in the suppression of some aspects of psychomotor activity. These postsynaptic receptors presumably belong to the D 3 receptor subtype.
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Similar content being viewed by others Explore related subjectsDiscover the latest articles and news from researchers in related subjects, suggested using machine learning. ReferencesAndén N-E (1980) Regulation of monoamine synthesis and utilization by receptors. In: Szekeres L (ed) Adrenergic activators and inhibitors, part I. Springer, Berlin Heidelberg New York Tokyo, p 429
Bouthenet ML, Souil E, Martres MP, Sokoloff P, Schartz JC (1991) Localization of dopamine D 3 receptors mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA. Brain Res 564: 203–219
Caine SB, Koob GF (1993) Modulation of cocaine self-administration in the rat through D-3 dopamine receptors. Science 260: 1814–1816
Carlsson A, Lindqvist M (1973) Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J Pharm Pharmacol 25: 437–440
Costall B, Lim SK, Naylor RJ (1981) Characterization of the mechanisms by which purported dopamine agonists reduce spontaneous locomotor activity of mice. Eur J Pharmacol 73: 175–188
Daly SA, Waddington JL (1993) Behavioural effects of the putative D-3 dopamine receptor agonist 7-OH-DPAT in relation to other “D-2-like” agonists. Neuropharmacology 32: 509–510
Johansson AM, Arvidsson LE, Hacksell U, Nilsson JLG, Svensson K, Hjorth S, Clark D, Carlsson A, Sanchez D, Andersson B, Wikström H (1985) Novel dopamine receptor agonists and antagonists with preferential action on autoreceptors. J Med Chem 28: 1049–1053
Lahti RA, Evans DL, Figur LM, Carrigan KJ, Moon MW, Hsi RS (1991) Dopamine D 2 receptor binding properties of [3H]U-86170, a dopamine receptor agonist. Eur J Pharmacol 202: 289–291
Lahti RA, Figur LM, Piercy MF, Ruppel PL, Evans DL (1992) Intrinsic activity determinations at the dopamine D 2 guanine nucleotide-binding protein-coupled receptor: utilization of receptor state binding affinities. Mol Pharmacol 42: 432–438
Landwehrmeyer B, Mengod G, Palacios JM (1993a) Dopamine D3 receptor mRNA and binding sites in human brain. Mol Brain Res 18: 187–192
Landwehrmeyer B, Mengod G, Palacios JM (1993b) Differential visualization of dopamine D 2 and D 3 receptor sites in rat brain. A comparative study using in situ hybridization histochemistry and ligand binding autoradiography. Eur J Neurosci 5: 145–153
Lévesque D, Diaz J, Pilon C, Martres MP, Giros B, Souil E, Schott D, Morgat JL, Schwartz JC, Sokoloff P (1992) Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N,-di-n-propyl-2-aminotetralin. Proc Natl Acad Sci USA 89: 8155–8159
Rubinstein M, Gershanik O, Stefano FJE (1988) Postsynaptic bimodal effect of sulpiride on locomotor activity induced by pergolide in catecholamine-depleted mice. Naunyn-Schmiedebergs Arch Pharmacol 337: 115–117
Snyder SH (1990) The dopamine connection. Nature 347: 121–122
Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347: 146–151
Sokoloff P, Andrieux M, Besançon R, Pilon C, Martres MP, Giros B, Schartz JC (1992) Pharmacology of human dopamine D3 receptors expressed in a mammalian cell line: comparison with D2 receptor. Eur J Pharmacol 225: 331–337
Ståhle L (1992) Do autoreceptors mediate dopamine agonist — induced yawning and suppression of exploration? A critical review. Psychopharmacology 106 (1): 1–13
Svensson K, Johansson AM, Magnusson T, Carlsson A (1986) (+)-AJ76 and (+)-UH 232: central stimulants acting as preferential dopamine autoreceptor antagonists. Naunyn-Schmiedebergs Arch Pharmacol 334: 234–245
Walters RJ, Roth RH (1976) Dopaminergic neurons: an in vivo system for measuring drug interactions with presynaptic receptors. Naunyn-Schmiedebergs Arch Pharmacol 296: 5–14
Waters N, Lagerqvist S, Löfberg L, Piercey M, Carlsson A (1993) The dopamine D 3- and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH 232; a microdialysis study. Eur J Pharmacol (in press)
Westerink BHC, Damsma G, De Vries JB, Koning H (1987) Dopamine re-uptake inhibitors show inconsistent effects on the in vivo release of dopamine as measured by intracerebral dialysis in the rat. Eur J Pharmacol 135: 123–128
N. Waters
Present address: Department of Pharmacology, University of Göteborg, Sweden
Department of Pharmacology, University of Göteborg, Sweden
K. Svensson, S. R. Haadsma-Svensson & A. Carlsson
Medicinal Chemistry Research, The Upjohn Company, Kalamazoo, MI, USA
S. R. Haadsma-Svensson
Chemical and Biological Screening, Upjohn Laboratories, The Upjohn Company, Kalamazoo, MI, USA
M. W. Smith
Waters, N., Svensson, K., Haadsma-Svensson, S.R. et al. The dopamine D3-receptor: A postsynaptic receptor inhibitory on rat locomotor activity. J. Neural Transmission 94, 11–19 (1993). https://doi.org/10.1007/BF01244979
Received: 13 August 1993
Accepted: 17 August 1993
Issue Date: February 1993
DOI: https://doi.org/10.1007/BF01244979
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