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Purine nucleoside — mediated immobility in mice: Reversal by antidepressants

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Abstract

In the forced swimming-induced immobility (despair) test model, adenosine, and 2-chloroadenosine treatment prolonged the immobilization period in mice. Dipyridamole, which is known to inhibit adenosine uptake, potentiated the adenosine effect. The purinoceptor antagonists caffeine and theophylline blocked purine nucleoside-induced enhancement of immobilization. Tricyclic antidepressants such as imipramine and desipramine, the MAO inhibitor tranylcypromine, and amphetamine, a psychostimulant, reversed purine nucleoside-induced immobility. On the other hand, quipazine, fluoxetine, and amitriptyline failed to reverse purine nucleosides-induced prolongation of immobility. None of the antidepressants in the doses investigated had any effect by themselves.

Reserpine also prolonged forced swimming-induced immobility in mice. The antidepressants fluoxetine and quipazine, but not methylxanthine pretreatment, reversed reserpine-induced immobility in this test model. These results indicate that adenosine and 2-chloroadenosine probably reduce norepinephrine outflow through their action on presynaptic purinoceptors on noradrenergic neurons and thereby cause prolongation of immobility in animals.

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References

  • Alfonso S, O'Brien GS (1971) Mechanism of enhancement of adenosine action by dipyridamole and lidoflazine in dogs. Arch Int Pharmacodyn Ther 194:181–186

    Google Scholar 

  • Carlsson A, Lindqvist M, Magnusson T (1957) 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180:1200

    Google Scholar 

  • Clanachan AS, Johns A, Paton DM (1977) Presynaptic inhibitory actions of adenine nucleotides and adenosine on neurotransmission in the rat vas deferens. Neuroscience 2:597–602

    Google Scholar 

  • Daly JW, Bruns RF, Snyder SH (1981) Adenosine receptors in the central nervous system: Relationship to the central actions of methylxanthines. Life Sci 28:2083–2097

    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

    Google Scholar 

  • Fuller RW, Wong DT (1977) Inhibition of serotonin reuptake. Fed Proc 36:2154–2158

    Google Scholar 

  • Haulica I, Ababei L, Branisteanu D, Topoliceanu F (1973) Preliminary data on the possible hypnogenic role of adenosine. J Neurochem 21:1019–1020

    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 35:679–680

    Google Scholar 

  • Hong E, Sancilio LF, Vargas R, Pardo EG (1969) Similarities between the pharmacological actions of quipazine and serotonin. Eur J Pharmacol 6:274–280

    Google Scholar 

  • Hopkins SV (1973) The potentiation of the action of adenosine on the guinea-pig heart. Biochem Pharmacol 22:341–348

    Google Scholar 

  • Kalsner S (1975) Adenosine and dipyridamole actions and interactions on isolated coronary artery strips of cattle. Br J Pharmacol 55:439–445

    Google Scholar 

  • Klabunde RE (1983) Dipyridamole inhibition of adenosine metabolism in human blood. Eur J Pharmacol 93:21–26

    Google Scholar 

  • Kulkarni SK, Mehta AK (1983) Purinoceptors: A new concept. Indian J Pharm Sci 45:150–157

    Google Scholar 

  • Kulkarni SK, Mehta AK (1984a) P1-purinoceptor antagonism by clonidine in the rat caecum. Life Sci 34:2273–2277

    Google Scholar 

  • Kulkarni SK, Mehta AK (1984b) The pharmacology of purine nucleosides and nucleotides. Drugs of Today 20:217–232

    Google Scholar 

  • Mehta AK, Kulkarni SK (1983) Effect of purinergic substances on rectal temperature in mice: Involvement of P1-purinoceptors. Arch Int Pharmacodyn Ther 264:180–186

    Google Scholar 

  • Mehta AK, Kulkarni SK (1984) Mechanism of potentiation by diazepam of adenosine response. Life Sci 34:81–86

    Google Scholar 

  • Mustafa SJ (1979) Effect of coronary vasodilator drugs on the uptake and release of adenosine in cardiac cells. Biochem Pharmacol 28:2617–2624

    Google Scholar 

  • Mustafa SJ (1980) Cellular and molecular mechanism(s) of coronary flow regulation by adenosine. Mol Cell Biochem 31:67–87

    Google Scholar 

  • Nagatani T, Sugihara T, Kodaira R (1984) The effect of diazepam and of agents which change GABAergic functions in immobility in mice. Eur J Pharmacol 97:271–275

    Google Scholar 

  • Natan LB, Chaillet P, Lecomte JM, Marçais H, Uchida G, Costentin J (1984) Involvement of endogenous enkephalins in the mouse behavioral despair' test. Eur J Pharmacol 97:301–304

    Google Scholar 

  • Paton DM (1981) Presynaptic neuromodulation mediated by purinergic receptors. In: Burnstock G (ed) Purinergic receptors. Chapman & Hall, London, pp 199–219

    Google Scholar 

  • Porsolt RD, Anton G, Blavat N, Jalfre M (1978a) Behavioural despair in rats: A new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391

    Google Scholar 

  • Porsolt RD, Bertin A, Blavet N, Deniel M, Jalfre M (1979) Immobility induced by forced swimming in rats: Effects of agents which modify central catecholamine and serotonin activity. Eur J Pharmacol 57:201–210

    Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977a) Behavioural despair in mice: A primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336

    Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1978b) Behavioural despair in rats and mice: Strain differences and the effects of imipramine. Eur J Pharmacol 51:291–294

    Google Scholar 

  • Porsolt RD, Le Pichon M, Jalfre M (1977b) Depression: A new animal model sensitive to antidepressant treatments. Nature 226:730–732

    Google Scholar 

  • Schechter MD, Chance WT (1979) Non-specificity of “Behavioural despair” as an animal model of depression. Eur J Pharmacol 60:139–142

    Google Scholar 

  • Stone TW (1981) Physiological roles for adenosine and adenosine-5′-triphosphate in the nervous system. Neuroscience 6:523–555

    Google Scholar 

  • Su C (1977) Adrenergic and noradrenergic vasodilator innervation. In: Carrier O Jr, Shibata S (eds) Factors influencing vascular reactivity. Igaku Shoin, Tokyo, pp 156–168

    Google Scholar 

  • Su C (1981) Purinergic receptors in blood vessels. In: Burnstock G (ed) Purinergic receptors. Chapman & Hall, London, pp 95–117

    Google Scholar 

  • Su C (1983) Purinergic neurotransmission and neuromodulation. Ann Rev Pharmacol Toxicol 23:397–411

    Google Scholar 

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Kulkarni, S.K., Mehta, A.K. Purine nucleoside — mediated immobility in mice: Reversal by antidepressants. Psychopharmacology 85, 460–463 (1985). https://doi.org/10.1007/BF00429665

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