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Effects of purine analogues on spontaneous alternation in mice

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Abstract

The Y-maze was used to examine the effects of purines acting at A1 and A2 adenosine receptors upon spontaneous alternation, a model of working memory, in mice. In support of previous work, scopolamine produced a loss of spontaneous alternation behaviour to the 0.5 chance level. The A1 receptor selective agonist N6-cyclopentyladenosine (CPA) did not change spontaneous alternation behaviour alone, but it prevented the decrease of spontaneous alternation scores produced by scopolamine. The A1 receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (CPX) blocked the effect of CPA in combination with scopolamine but had no effect alone. The A2 receptor selective agonist (N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA), and the A2 receptor selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) had no effect of alternation behaviour alone and did not modify the effect of scopolamine. The results indicate the ability of A1 but not A2 receptor activation to modify working memory deficits induced by scopolamine, but suggest that endogenous adenosine does not normally participate in working memory processes.

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References

  • Ahlijanian MK, Takemori AE (1985) Effects of R-PIA and caffeine on nociception and morphine-produced analgesia, tolerance and dependence in mice. Eur J Pharmacol 112:171–179

    Article  PubMed  Google Scholar 

  • Anisman H (1975) Dissociation of disinhibitory effects of scopolamine: strain and task factors. Pharmacol Biochem Behav 3:613–618

    Article  PubMed  Google Scholar 

  • Barraco RA, Coffin VL, Altman HJ, Phillis JW (1983) Central effects of adenosine analogs on locomotor activity in mice and antagonism of caffeine. Brain Res 272:392–395

    Article  PubMed  Google Scholar 

  • Barraco RA, Swanson TH, Phillis JW, Berman RF (1984) Anticonvulsant effects of adenosine analogues on amygdalakindled seizures in rats. Neurosci Lett 46:317–322

    Article  PubMed  Google Scholar 

  • Barraco RA, Martens KA, Parizon M, Normile HJ (1993) Adenosine A2a receptors in the nucleus accumbens mediate locomotor depression. Brain Res Bull 31:397–404

    Article  PubMed  Google Scholar 

  • Baumgold J, Nikodijevic O, Jacobson KA (1992) Penetration of adenosine antagonists into mouse brain as determined by ex vivo binding. Biochem Pharmacol 43:889–894

    Article  PubMed  Google Scholar 

  • Beninger RJ, Jhamandas K, Boegman RJ, El-Defrawy SR (1986) Effect of scopolamine and unilateral lesions of the forebrain on T-maze spatial discrimination and alternation in rats. Pharmacol Biochem Behav 24:1353–1360

    Article  PubMed  Google Scholar 

  • Bruns RF, Fergus JH, Badger EW, Bristol JA, Santay LA, Hartman JD, Hays SJ Huang CC (1987) Binding of the A1-selective adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes. Arch Pharmacol 335:59–63

    Article  Google Scholar 

  • Coffin VL, Spealman, RD (1985) Modulation of the behavioural effects of clordiazepoxide by methylxanthines and analogues of adenosine in squirrel monkeys. J Pharmacol Exp Ther 235:724–728

    PubMed  Google Scholar 

  • Coffin VL Spealman RD (1987) Behavioural and cardiovascular effects of analogues of adenosine in cynomolgus monkeys. J Pharmacol Exp Ther 241:76–83

    PubMed  Google Scholar 

  • Crawley JN, Patel J, Marangos PJ (1981) Behavioural characterization of two long lasting adenosine analogues: sedative properties and interaction with diazepam. Life Sci. 29:2623–2630

    Article  PubMed  Google Scholar 

  • Dauge V, Derrien M, Blanchard JC, Roques BP (1992) The selective CCK-B antagonist BC264 injected into the anterolateral part of the nucleus accumbens, reduces the spontaneous alternation behaviour of rats. Neuropharmacology 31:67–75

    Article  PubMed  Google Scholar 

  • Dennis WJ (1939) Spontaneous alternation in rats as an indicator of the persistence of stimulus traces. J Comp Psychol 28:305–312

    Google Scholar 

  • Douglas RJ Isaacson RL (1966) Spontaneous alternation and scopolamine. Psychonom Sci 4:283–284

    Google Scholar 

  • Drachman DA (1977) Memory and cognitive function in man: does the cholinergic system have a specific role? Neurology 27:783–790

    PubMed  Google Scholar 

  • Dragunow M (1988) Purinergic mechanisms in epilepsy. Prog Neurobiol 31:85–108

    Article  PubMed  Google Scholar 

  • Drew WG, Miller LL Baugh EL (1973) Effects of THC, LSD-25 and scopolamine on continuous, spontaneous alternation in the Y-maze. Psychopharmacology 32:171–182

    Article  Google Scholar 

  • Dunbar GL, Rylett RJ, Schmidt BM, Sinclair RC, Williams LR (1993) Hippocampal choline acetyltransferase activity correlates with spatial learning in aged rats. Brain Res 604:266–272

    Article  PubMed  Google Scholar 

  • Dunwiddie TV, Worth T (1982) Sedative and anticonvulsant effects of adenosine analogs in mouse and rat. J Pharmacol Exp Ther 220:70–76

    PubMed  Google Scholar 

  • Durcan MJ, Morgan PF (1989) NECA-induced hypomotility in mice: evidence for a predominantly central site of action. Pharmacol Biochem Behav 32:487–490

    Article  PubMed  Google Scholar 

  • Egger GJ, Livesey PJ, Dawson RG (1973) Ontogenetic aspects of central cholinergic involvement in spontaneous alternation behaviour. Dev Psychobiol 6:289–299

    Article  PubMed  Google Scholar 

  • Glanzer M (1953) Stimulus satiation: an explanation of spontaneous alternation and related phenomena. Psychol Rev 60:257–268

    PubMed  Google Scholar 

  • Glasky AJ, Melchior CL, Pirzadeh B, Heydari N, Ritzmann RF (1994) Effect of AIT-082, a purine analog, on working memory in normal and aged mice. Pharmacol Biochem Behav 47:325–329

    Article  PubMed  Google Scholar 

  • Grette Lydon R (1994) Cholinergic neurones and memory: and overview and historical perspective. In: Stone TW (ed) CNS neurotransmitters and neuromodulators, vol. 1: acetylcholine. CRC Press, Boca Raton, Chapter 14

    Google Scholar 

  • Griebel G, Misslin R, Vogel E (1991a) Behavioural effects of selective A2 adenosine receptor antagonists, CGS 21197 and CGS 22706, in mice. NeuroReport 2:139–140

    PubMed  Google Scholar 

  • Griebel G, Saffroy-Spittler M, Misslin R, Remmy D, Vogel E, Bourguignon J-J (1991b) Comparison of the behavioural effects of an adenosine A1/A2 receptor antagonist CGS 15943A, and an A1-selective antagonist, DPCPX. Psychopharmacology 103:541–544

    Article  PubMed  Google Scholar 

  • Hall JL, Gonder-Frederick LA, Chewning WW, Silveira J, Gold PE (1989) Glucose enhancement of memory in young and aged humans. Neuropsychology 27:1129–1138

    Article  Google Scholar 

  • Holmgren M, Hednar T, Nordberg G, Mellstrand T (1983) Antinociceptive effects in the rat of an adenosine analogue N6-phenylisopropyladenosine. J Pharm Pharmacol 35:679

    PubMed  Google Scholar 

  • Holtzman SG (1991) CGS 15943, a nonxanthine adenosine receptor antagonist: effects on locomotor activity of nontolerant and caffeine-tolerant rats. Life Sci 49:1563–1570

    Article  PubMed  Google Scholar 

  • Itoh J, Ukai M, Kameyama T (1993) Dynorphin A(1–13) markedly improves scopolamine-induced impairment of spontaneous alternation performance in mice. Eur J Pharmacol 236:341–345

    Article  PubMed  Google Scholar 

  • Jacobson KA, Nikodijevic O, de la Cruz D, Daly JW (1991) APEC, an A2-selective adenosine agonist, is a more potent locomotor depressant than N6-cyclohexyladenosine. Nucleosides Nucleotides 10:1211–1212

    Google Scholar 

  • Janusz CA, Berman RF (1992) The A2-selective adenosine analog CGS 21680, depresses locomotor activity but does not block amygdala kindled seizures in rats. Neurosci Lett 141:247–250

    Article  PubMed  Google Scholar 

  • Janusz CA, Berman RF (1993) Adenosinergic modulation of the EEG and locomotor effects of the A2 agonist, CGS 21680 Pharmacol Biochem Behav 45:913–919

    Article  PubMed  Google Scholar 

  • Kokkinidis L, Anisman H (1976) Interaction between cholinergic and catecholaminergic agents in a spontaneous alternation task. Psychopharmacology 48:261–265

    Article  PubMed  Google Scholar 

  • Lohse MJ, Klotz KN, Lindenborn-Fotinos J, Reddington M, Schwab U, Olsson RA (1987) 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) — a selective high affinity antagonist radioligand for A1 adenosine receptors. Arch Pharmacol 336:204–210

    Article  Google Scholar 

  • Manning CA, Hall JL, Gold PE (1990) Memory enhancement by glucose in aged humans. Psychol Sci 1:307–311

    Google Scholar 

  • Martin GE, Rossi DJ, Jarvis MF (1993) Adenosine agonists reduce conditioned avoidance responding in the rat. Pharmacol Biochem Behav 45:951–958

    Article  PubMed  Google Scholar 

  • Nikodijevic O, Sparges R, Daly JW, Jacobson KA (1991) Behavioural effects of A1 and A2-selective adenosine agonists and antagonists: evidence for synergism and antagonism. J Pharmacol Exp Ther 259:286–294

    PubMed  Google Scholar 

  • Normile HJ, Barraco RA (1991) N6-cyclopentyladenosine impairs passive avoidance retention by selective action at A1 receptors. Brain Res Bull 27:101–104

    Article  PubMed  Google Scholar 

  • Ohno M, Yamamoto T, Watanabe S (1994) Blockade of hippocampal M1 muscarinic receptors impairs working memory performance of rats. Brain Res 650:260–266

    Article  PubMed  Google Scholar 

  • Palmour RM, Lipowski CJ, Simon CK, Ervin FR (1989) Adenosine analogues inhibit fighting in isolated male mice. Life Sci 44:1293–1299

    Article  PubMed  Google Scholar 

  • Parada-Turska J, Turski WA (1990) Excitatory amino acid antagonists and memory: effect of drugs acting at NMDA receptors in learning and memory tasks. Neuropharmacology 29:1111–1116

    Article  PubMed  Google Scholar 

  • Post C (1984) Anti-nociceptive effects in mice after intrathecal injections of NECA. Neurosci Lett 51:325–330

    Article  PubMed  Google Scholar 

  • Sarter M, Bodewitz G, Stephens DN (1988) Attenuation of scopolamine induced impairment of spontaneous alternation behaviour by antagonist but not inverse agonist and agonist b-carbolines. Psychopharmacology 94:491–495

    Google Scholar 

  • Schingnitz G, Kufner-Muhl U, Ensinger H, Lehr E, Kuhn FJ (1991) Selective A1-antagonists for treatment of cognitive deficits. Nucleosides Nucleotides 10:1067–1076

    Google Scholar 

  • Snyder SH, Katins JS, Annau Z, Bruns RF, Daly JW (1981) Adenosine receptors and the actions of the methylxanthines. Proc Natl Acad Sci 78:3260–3264

    PubMed  Google Scholar 

  • Spealman RD, Coffin VL (1986) Behavioural effects of adenosine analogues in squirrel monkeys: relation to adenosine A2 receptors. Psychopharmacology 90:419–421

    Google Scholar 

  • Spencer DG, Lal H (1983) Effects of anticholinergic drugs on learning and memory. Drug Dev Res 3:489–502

    Article  Google Scholar 

  • Spencer DG, Pontecorvo MJ, Heise GA (1985) Central cholinergic inolvement in working memory: effects of scopolamine on continuous nonmatching and discrimination performance in the rat. Behav Neurosci 99:1049–1065

    Article  PubMed  Google Scholar 

  • Squire LR (1969) Effect of pre-trial and post-trial administration of cholinergic and anticholinergic drugs on spontaneous alternation. J Comp Physiol Psychol 74:41–45

    Google Scholar 

  • Stone TW, Simmonds HA (1991) Purines: basic and clinical aspects. Kluwer Press, Dordrecht

    Google Scholar 

  • Stone WS Walser B, Gold SD, Gold PE (1991) Scopolamine and morphine induced impairments of spontaneous alternation performance in mice: reversal with glucose and with cholinergic and adrenergic agonists. Behav Neurosci 105:264–271

    Article  PubMed  Google Scholar 

  • Stone WS, Rudd RJ, Gold PE (1992) Glucose attenuation of scopolamine and age induced deficits in spontaneous alternation behaviour and regional brain [3H]-2-deoxyglucose uptake in mice. Psychobiology 20:270–279

    Google Scholar 

  • Swonger AK, Rech RH (1972) Serotonergic and cholinergic involvement in habituation of activity and spontaneous alternation of rats in a Y maze. J Comp Physiol Psychol 81:509–522

    PubMed  Google Scholar 

  • Tobe A, Egawa M, Nagai R (1983) Effect of MCI-2016 on the scopolamine induced deficit of spontaneous alternation behaviour in rats. Jpn J Pharmacol 33:775–784

    PubMed  Google Scholar 

  • Troster AI, Beatty WW, Staton RD, Rorabaugh AG (1989) Effect of scopolamine on anterograde and remote memory in humans. Psychobiology 17:17–18

    Google Scholar 

  • Walker DL Gold PE (1991) Effect of the novel NMDA antagonist NPC 12626 on long-term potentiation, learning and memory. Brain Res 549:213–221

    Article  PubMed  Google Scholar 

  • Walker DL, Gold PE (1992) Impairment of spontaneous alternation performance by an NMDA antagonist: attenuation with non-NMDA treatments. Behav Neural Biol 58:69–71

    Article  PubMed  Google Scholar 

  • Warburton DM, Heise GA (1972) Effects of scopolamine on spatial double alternation in rats. J Comp Hhysiol Psychol 81:523–532

    Google Scholar 

  • Williams M, Braunwalder A, Erickson TE (1986) Evaluation of the binding of the A1-selective adenosine radioligand, cyclopentyladenosine to rat brain tissue. Arch Pharmacol 332:179–183

    Article  Google Scholar 

  • Willig F, Van de Velde D, Laurent J, M'Harzi M, Delacour J (1992) The Roman strains of rats as a psychogenetic tool for pharmacological investigation of working memory: example with RU 41656. Psychopharmacology 107:415–424

    PubMed  Google Scholar 

  • Winsky L, Harvey JA (1986) Retardation of associative learning in the rabbit by an adenosine analogue as measured by classical conditioning of the nictitating membrane response. J Neurosci 6:2684

    PubMed  Google Scholar 

  • Yarbrough GG, McGuffin-Clineschmidt TC (1981) In vivo behavioural assessment of CNS purinergic receptors. Eur J Pharmacol 76:137–144

    Article  PubMed  Google Scholar 

  • Zarrindast MR, Bijan S (1994) Effects of adenosine receptor agonists and antagonists on acquisition of passive avoidance learning. Eur J Pharmacol 256:233–239

    Article  PubMed  Google Scholar 

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Hooper, N., Fraser, C. & Stone, T.W. Effects of purine analogues on spontaneous alternation in mice. Psychopharmacology 123, 250–257 (1996). https://doi.org/10.1007/BF02246579

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