Abstract
In unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats, a rodent model of Parkinson's disease (PD), the adenosine A2A receptor antagonist SCH 58261 significantly increased (+180%, p < .01) the number of rotations induced by a low dose of quinpirole (a dopamine D2 receptor agonist), while it did not significantly modify the effects of a comparably low dose of SKF 38393 (a dopamine D1 receptor agonist). The dose-dependent potentiating effects of SCH 58261 on quinpirole-induced turning were similar in caffeine-treated rats (1 g/l in drinking water over 14 days) and control animals (tap water). The selective potentiating effects of SCH 58261 on D2-dependent turning confirm the existence of a potent and specific A2A/D2 receptor-receptor interaction. The persistence of the potentiating effects of SCH 58261 after chronic caffeine intake suggests that no tolerance should develop towards the antiparkinsonian effects of adenosine A2A receptor antagonists with chronic treatment.
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References
Albin RL, Young AB, Penney JB . (1989): The functional anatomy of basal ganglia disorders. Trends Neurosci 12: 366–375
Alexander GR, Crutcher MD . (1990): Functional architecture and basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13: 266–271
Brown SJ, James S, Reddington M, Richardson PJ . (1990): Both A1 and A2a purine receptors regulate striatal acetylcholine release. J Neurochem 55: 31–37
Dasgupta S, Ferré S, Kull B, Hedlund PB, Finnman UB, Ahlberg S, Arenas E, Fredholm BB, Fuxe K . (1996): Adenosine A2A receptor modulate the binding characteristics of dopamine D2 receptors in stably cotransfected fibroblast cells. Eur J Pharmacol 316: 325–331
Fenu S, Pinna A, Ongini E, Morelli M . (1997): Adenosine A2A receptor antagonism potentiates L-DOPA-induced turning behaviour and c-fos expression in 6-hydroxydopamine-lesioned rats. Eur J Pharmacol 321: 143–147
Ferré S, Herrera-Marschitz M, Grabowska-Andén M, Casa M, Ungerstedt U, Andén NE . (1991a): Postsynaptic dopamine/adenosine interaction. I. Adenosine analogues inhibit dopamine D 2-mediated behaviour in short-term reserpinized mice. Eur J Pharmacol 192: 25–29
Ferré S, Von Euler G, Johansson B, Fredholm B, Fuxe K . (1991b): Stimulation of high affinity adenosine A-2 receptors decreases the affinity of dopamine D-2 receptors in rat striatal membranes. Proc Natl Acad Sci USA 88: 7238–7241
Ferré S, Fuxe K . (1992): Dopamine denervation leads to an increase in the intramembrane interactions between adenosine A2 and dopamine D2 receptors in the neostriatum. Brain Res 594: 124–130
Ferré S, Fuxe K, Von Euler G, Johansson B, Fredholm BB . (1992): Adenosine-dopamine interactions in the brain. Neuroscience 51: 501–512
Ferré S, O'Connor WT, Fuxe K, Ungerstedt U . (1993): The striopallidal neuron: a main locus for adenosine-dopamine interactions in the brain. J Neurosci 13: 5402–5406
Ferré S, Fredholm BB, Morelli M, Popoli P, Fuxe K . (1997): Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci 20: 482–487
Ferré S, Popoli P, Rimondini R, Reggio R, Kehr J, Fuxe K . (1999): Adenosine A2A and group I metabotropic glutamate receptors synergistically modulate the binding characteristics of dopamine D2 receptors in the rat striatum. Neuropharmacol 38: 129–140
Fink JS, Weaver DR, Rivkees SA, Peterfreund RA, Pollack A, Adler DM, Reppert SM . (1992): Molecular cloning of the rat A2 adenosine receptors: selective co-expression with D2 dopamine receptors in rat striatum. Mol Brain Res 14: 186–195
Garrett BE, Holtzman SG . (1994): Caffeine cross-tolerance to the selective dopamine D1 and D2 receptor agonists but not to their synergistic interaction. Eur J Pharmacol 262: 65–75
Garrett BE, Holtzman SG . (1995a): Does adenosine receptor blockade mediate caffeine-induced rotational behaviour?. J Pharmacol Exp Ther 274: 207–214
Garrett BE, Holtzman SG . (1995b): The effects of dopamine agonists on rotational behavior in non-tolerant and caffeine-tolerant rats. Behav Pharmacol 6: 843–851
Gerfen CR, Engber TM, Mahan L, Susel Z, Chase TN, Monsma FJ, Sibley DR . (1990): D1 and D2 dopamine receptor-regulated gene expression of strionigral and striopallidal neurons. Science 250: 1429–1432
Holtzman SG, Mante S, Minneman KP . (1991): Role of adenosine receptors in caffeine tolerance. J Pharmacol Exp Ther 256: 62–68
Kanda T, Jackson MJ, Smith LA, Pearce RKB, Nakamura J, Kase H, Kuwana Y, Jenner P . (1998): Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol 43: 507–513
Jacobson KA, Von Lubitz DKJE, Daly JW, Fredholm BB . (1996): Adenosine receptor ligands: diferences with acute versus chronic treatment. Trends Pharmacol Sci 17: 108–113
Jin S, Johansson B, Fredholm BB . (1993): Effects of adenosine A1 and A2 receptor activation on electrically evoked dopamine and acetylcholine release from rat striatal slices. J Pharmacol Exp Ther 267: 801–808
Morelli M, Fenu S, Pinna A, Di Chiara G . (1994): Adenosine A2 receptors interact negatively with dopamine D1 and D2 receptors in unilaterally 6-hydroxydopamine-lesioned rats. Eur J Pharmacol 251: 21–25
Morelli M, Pinna A, Wardas J, Di Chiara G . (1995): Adenosine A2 receptors stimulate c-fos expression in striatal neurons of 6-hydroxydopamine-lesioned rats. Neuroscience 67: 49–55
Nikodijevic O, Jacobson KA, Daly JW . (1993a): Locomotor activity in mice during chronic treatment with caffeine and withdrawal. Pharmacol Biochem Behav 44: 199–216
Nikodijevic O, Jacobson KA, Daly JW . (1993b): Effects of combinations of methylxanthines and adenosine analogs on locomotor activity in control and chronic caffeine-treated mice. Drug Dev Res 30: 104–110
Ongini E, Fredholm BB . (1996): Pharmacology of adenosine A2A receptors. Trends Pharmacol Sci 17: 364–372
Pinna A, Di Chiara G, Wardas J, Morelli M . (1996): Blockade of A2a receptors positively modulates turning behaviour and c-Fos expression induced by D1 agonists in dopamine-denervated rats. Eur J Neurosci 8: 1176–1181
Pollack AE, Fink JS . (1995): Adenosine antagonists potentiate D2-dopamine-dependent activation of Fos in the striopallidal pathway. Neuroscience 68: 721–728
Pollack AE, Fink JS . (1996): Synergistic interaction between an adenosine antagonist and a D1 dopamine agonist on rotational behavior and striatal c-Fos induction in 6-hydroxydopamine-lesioned rats. Brain Res 743: 124–130
Popoli P, Betto P, Reggio R, Ricciarello G . (1995): Adenosine A2A receptor stimulation enhances striatal extracellular glutamate levels in rats. Eur J Pharmacol 287: 215–217
Popoli P, Reggio R, Pèzzola A, Fuxe K, Ferré S . (1998): Adenosine A1 and A2 receptor antagonists stimulate motor activity: evidence for an increased effectiveness in aged rats. Neurosci Lett 251: 201–204
Richardson PJ, Kase H, Jenner PG . (1998): Adenosine A2A receptor antagonists as new agents for the treatment of Parkinson's disease. Trends Pharmacol Sci 18: 338–344
Schiffmann SN, Jacobs O, Vanderhaeghen JJ . (1991): Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. J Neurochem 57: 1062–1067
Schwarting PKW, Huston JP . (1996): The unilateral 6-hydroxydopamine lesion model in behavioural brain research. Analysis of functional deficits, recovery and treatments. Progr Neurobiol 50: 275–331
Svenningsson P, Fredholm BB . (1997): Caffeine mimics the effect of a dopamine D2/3 receptor agonist on the expression of immediate early genes in globus pallidus. Neuropharmacol 36: 1309–1317
Svenningsson P, Le Moine C, Kull B, Sunahara R, Bloch B, Fredholm BB . (1997a): Cellular expression of adenosine A2A receptor messenger RNA in the rat central nervous system with special reference to dopamine innervated areas. Neuroscience 80: 1171–1185
Svenningsson P, Nomikos G, Ongini E, Fredholm BB . (1997b): Antagonism of adenosine A2A receptors underlies the behavioural activating effect of caffeine and is associated with reduced expression of messenger RNA for NGFI-A and NGFI-B in caudate-putamen and nucleus accumbens. Neuroscience 79: 753–764
Ungerstedt U . (1971): Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigrostriatal dopamine system in the rat brain. Acta Physiol Scand 82 Suppl. 367: 69–93
Zocchi C, Ongini E, Conti A, Monopoli A, Negretti A, Baraldi PG, Dionisotti S . (1996): The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist. J Pharmacol Exp Ther 276: 398–404
Acknowledgements
The authors thank Prof. Kjell Fuxe and Dr. Sergi Ferré (Department of Neuroscience, Karolinksa Institute, Stockholm, Sweden) for helpful discussions throughout the study and Dr. Ennio Ongini (Schering Plough, Milan) for generously providing SCH 58261.
This work was supported by a coordinated European BIOMED 2 project (BM4-CT96-0238).
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Popoli, P., Reggio, R. & Pèzzola, A. Effects of SCH 58261, an Adenosine A2A Receptor Antagonist, on Quinpirole-Induced Turning in 6-Hydroxydopamine-Lesioned Rats: Lack of Tolerance after Chronic Caffeine Intake. Neuropsychopharmacol 22, 522–529 (2000). https://doi.org/10.1016/S0893-133X(99)00144-X
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DOI: https://doi.org/10.1016/S0893-133X(99)00144-X
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