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Biphasic effects of dopamine D-2 receptor agonists on sleep and wakefulness in the rat

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Abstract

The effects of the dopamine (DA) receptor agonists apomorphine, bromocriptine and pergolide were compared with those produced by a DA receptor antagonist, haloperidol, in rats implanted with electrodes for chronic sleep recordings. Apomorphine (0.025–2.0 mg/kg) and bromocriptine (0.25–6.0 mg/kg) induced biphasic effects such that low doses decreased wakefulness (W) and increased slow wave sleep (SWS) and REM sleep (REMS), while large doses induced opposite effects. The effects of pergolide (0.05–0.5 mg/kg) on W and SWS were also biphasic, while REMS was suppressed over the range of dosages given. At 0.040 mg/kg, haloperidol increased W, while at 0.160 mg/kg it produced the opposite effect. Pretreatment with haloperidol (0.020 mg/kg) in a dose which preferentially acts at presynaptic sites reversed the effects of low doses of apomorphine, bromocriptine or pergolide on sleep and W. However, the compound differed substantially in its ability to block agonist effects.

The increase in sleep after low doses of apomorphine, bromocriptine or pergolide could be related to activation of presynaptic D-2 receptors located on DA axons of mesolimbic and mesocortical systems. In addition, inhibition of norepinephrine and acetylcholine neurons having inhabitory D-2 receptors could contribute to the increase of sleep after small doses of the DA agonists.

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References

  • Altier H, Moldes M, Monti JM (1975) The actions of dihydroxyphenylalanine and dihydroxyphenylserine on the sleep-wakefulness cycle of the rat after peripheral decarboxylase inhibition. Br J Pharmacol 54:101–106

    Google Scholar 

  • Anden NE, Grabowska-Andén M, Liljenberg B (1983) Demonstration of autoreceptors on dopamine neurons in different brain regions of rats treated with gammabutyrolactone. J Neural Transm 58:143–152

    Google Scholar 

  • Baudry M, Costentin J, Marcais H, Martres MP, Protais P, Schwartz JC (1977) Decreased responsiveness to low doses of apomorphine after dopamine agonists and the possible involvement of hyposensitivity of dopamine “autoreceptors”. Neurosci Lett 4:203–207

    Google Scholar 

  • Berger B, Verney C, Alvarez C, Vigny A, Hell KB (1985) New dopaminergic terminal fields in the motor, visual (area 18b) and retrosplenial cortex in the young and adult rat. Immunocytochemical and catecholamine histochemical analysis. Neuroscience 15:983–998

    Google Scholar 

  • Brambilla F, Scarone S, Pugnetti L, Massironi R, Penati G, Nobile P (1983) Bromocriptine therapy in chronic schizophrenia: effects on symptomatology, sleep patterns, and prolactin response to stimulation. Psychiatry Res 8:159–169

    Google Scholar 

  • Carter CJ, Pycock CJ (1980) Behavioral and biochemical effects of dopamine and noradrenaline depletion within the medial prefrontal cortex of the rat. Brain Res 192:163–172

    Google Scholar 

  • Cianchetti C, Masala C, Magnoni A, Gessa GL (1980) Suppression of REM and delta sleep by apomorphine in man: a dopamine mimetic effect. Psychopharmacology 67:61–65

    Google Scholar 

  • Di Chiara G, Porceddu ML, Vargiu L, Argiolas A, Gessa GL (1976) Evidence for dopamine receptors mediating sedation in the mouse brain. Nature 264:564–566

    Google Scholar 

  • Fuller RW, Clemens JA, Hynes MD (1982) Degree of selectivity of pergolide as an agonist at presynaptic versus postsynaptic dopamine receptors: implications for prevention of treatment of tardive dyskinesia. J Clin Psychopharmacol 2:371–375

    Google Scholar 

  • Galzin AM, Dubocovich ML, Langer SZ (1982) Presynaptic inhibition by dopamine receptor agonists of noradrenergic neurotransmission in the rabbit hypothalamus. J Pharmacol Exp Ther 221:461–471

    Google Scholar 

  • Gaillard JM (1985) Neurochemical regulation of the states of alertness. Ann Clin Res 17:175–184

    Google Scholar 

  • Gillin JC, van Kammen DP, Post RM, Sitaran N, Wyatt RJ, Bunney WE (1981) What is the role of dopamine in the regulation of sleep-wake activity. In: Corsini GU, Gessa GL (eds) Apomorphine and other dopaminomimetics, vol II. Raven Press, New York, pp 157–164

    Google Scholar 

  • Herrera-Marschitz M, Ungerstedt U (1984) Evidence that striatal efferents relate to different dopamine receptors. Brain Res 323:269–278

    Google Scholar 

  • Hopkins DA, Niessen LW (1976) Substantia nigra projections to the reticular formation, superior colliculus and central gray in the rat, cat and monkey. Neurosci Lett 2:253–259

    Google Scholar 

  • Hyttel J, Christensen AV (1983) Biochemical and pharmacological differentiation of neuroleptic effect of dopamine D-1 and D-2 receptors. J Neural Transm 18:157–164

    Google Scholar 

  • Jiang DH, Reches A, Wagner HR, Fahn S (1984) Biochemical and behavioral evaluation of pergolide as a dopamine agonist in the rat brain. Neuropharmacology 23:295–301

    Google Scholar 

  • Kaiser C, Jain T (1985) Dopamine receptors: functions, subtypes and emerging concepts. Med Res Rev 5:145–229

    Google Scholar 

  • Kendler KS, Bracha HS, Davis KL (1982) Dopamine autoreceptor and postsynaptic receptor blocking potency of neuroleptics. Eur J Pharmacol 79:217–223

    Google Scholar 

  • Koella WP (1985) Neurotransmitters and sleep — a synthesis. In: Koella WP, Rüther E, Schulz H (eds) Sleep '84. Fischer, Stuttgart, New York, pp 28–39

    Google Scholar 

  • Langer SZ (1981) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362

    Google Scholar 

  • Langer SZ, Arbilla S, Kamal L (1980) Autoregulation of noradrenaline and dopamine release through presynaptic receptors. In: Littauer UZ, Dudai Y, Silman I, Teichberg VI, Vogel Z (eds) Neurotransmitters and their receptors. Wiley, New York, pp 7–21

    Google Scholar 

  • Langer SZ, Arbilla S, Kamal L, Cantrill R (1983) Peripheral and central dopamine receptors modulating the release of neurotransmitters. Acta Pharm Suec [Suppl] 1:108–117

    Google Scholar 

  • McRae-Degueurce A, Milon H (1983) Serotonin and dopamine afferents to the rat locus coeruleus: biochemical study after lesioning of the ventral mesencephalic tegmental-A10 region and the raphé dorsalis. Brain Res 263:344–347

    Google Scholar 

  • Mereu GP, Scarnati E, Pagliettu E, Pellegrini Guarantotti B, Chessa P, Di Chiara G, Gessa GL (1979) Sleep induced by low doses of apomorphine in rats. Electroencephalogr Clin Neurophysiol 46:214–219

    Google Scholar 

  • Monti JM (1979) The effects of neuroleptics with central dopamine and noradrenaline receptor blocking properties in the l-dopa and (+)-amphetamine-induced waking EEG in the rat. Br J Pharmacol 67:87–91

    Google Scholar 

  • Monti JM (1982) Catecholamines and the sleep-wake cycle. I. EEG and behavioral arousal. Life Sci 30:1145–1157

    Google Scholar 

  • Pasquier DA, Kemper TL, Forbes WB, Morgane PJ (1977) Dorsal raphe, substantia nigra and locus coeruleus: interconnections with each other and the neostriatum. Brain Res Bull 2:323–339

    Google Scholar 

  • Radulovacki M, Wojcik WJ, Fornal C (1979) Effects of bromocriptine and α-flupenthixol on sleep in REM sleep deprived rats. Life Sci 24:1705–1712

    Google Scholar 

  • Radulovacki M, Brodie M, Walovitch R, Yanik G (1981) Bromocriptine, dihydroergotoxine and sleep in rats: effects of repeated administration. Gerontology 27:152–157

    Google Scholar 

  • Scatton B (1982) Effect of dopamine agonists and neurologic agents on striatal acetylcholine transmission in the rat. Evidence against dopamine receptor multiplicity. J Pharmacol Exp Ther 220:197–202

    Google Scholar 

  • Simon H, Le Moal M, Callas A (1979) Efferents and afferents of the ventral tegmental A10 region studied after local injection of 3H-leucine and horseradish peroxidase. Brain Res Bull 9:321–353

    Google Scholar 

  • Steinfels GF, Heym J, Strecker RE, Jacobs BL (1983) Behavioral correlates of dopaminergic unit activity in freely moving cats. Brain Res 258:217–228

    Google Scholar 

  • Stoof JC, Kebabian JW (1984) Two dopamine receptors: biochemistry, physiology and pharmacology. Life Sci 35:2281–2296

    Google Scholar 

  • Strömbon U (1977) Antagonism by haloperidol of locomotor depression induced by small doses of apomorphine. J Neural Transm 40:191–194

    Google Scholar 

  • Sumners C, De Vries JB, Horn AS (1981) Behavioral and neurochemical studies on apomorphine-induced hypomotility in mice. Neuropharmacology 20:1203–1208

    Google Scholar 

  • Thierry AM, Tassin JP, Glowinski J (1984) Biochemical and electrophysiological studies of the mesocortical dopamine system. In: Desearries L, Reader TA, Jasper HH (eds) Monoamine innervation of cerebral cortex. Liss, New York, pp 233–261

    Google Scholar 

  • Trulson ME (1985) Simultaneous recording of substantia nigra neurons and voltametric release of dopamine in the caudate of behaving cats. Brain Res Bull 15:221–223

    Google Scholar 

  • Trulson ME, Preussler DW (1984) Dopamine-containing ventral tegmental area neurons in freely moving cats: Activity across the sleep-waking cycle and response to stress. Exp Neurol 83:367–377

    Google Scholar 

  • Wauquier A (1985) Dopamine: its active and permissive roles in sleep-wakefulness. In: Koella WP, Rüther E, Schulz H (eds) Sleep '84. Fischer, Stuttgart, New York, pp 14–16

    Google Scholar 

  • Yarbrough GG, Mcguffin-Clineschmidt J, Singh DK, Haubrich DR, Bendesky RJ, Martin GE (1984) Electrophysiological, biochemical and behavioral assessment of dopamine autoreceptor activation by a series of dopamine agonists. Eur J Pharmacol 99:73–78

    Google Scholar 

  • Zar JH (1974) Biostatistical analysis. Prentice-Hall, Englewood Cliffs

    Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, School of Medicine, Hospital de Clínicas P1, Montevideo, Uruguay

    Jaime M. Monti, Marjorie Hawkins, Héctor Jantos, Luisa D'Angelo & Mónica Fernández

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  1. Jaime M. Monti
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  2. Marjorie Hawkins
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  3. Héctor Jantos
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  4. Luisa D'Angelo
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  5. Mónica Fernández
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Monti, J.M., Hawkins, M., Jantos, H. et al. Biphasic effects of dopamine D-2 receptor agonists on sleep and wakefulness in the rat. Psychopharmacology 95, 395–400 (1988). https://doi.org/10.1007/BF00181955

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  • DOI: https://doi.org/10.1007/BF00181955

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