Psychopharmacology

, Volume 88, Issue 2, pp 141–146 | Cite as

Central noradrenaline depletion antagonizes aspects ofd-amphetamine-induced hyperactivity in the rat

  • Trevor Archer
  • Anders Fredriksson
  • Gösta Jonsson
  • Tommy Lewander
  • Abdul K. Mohammed
  • Svante B. Ross
  • Ulf Söderberg
Original Investigations

Abstract

The effects of noradrenaline (NA) depletion upon amphetamine-induced hyperactivity were examined in five experiments. Central NA depletion via either systemic DSP4 or neonatal 6-OHDA antagonised the amphetamine-induced (2 mg/kg SC) increase in rearing behaviour, whereas lesions of the dorsal noradrenergic bundle using 6-hydroxydopamine antagonised the increase in locomotor activity. Peripheral NA depletion following systemic 6-hydroxydopamine to adult rats did not cause any changes in motor activity after acute amphetamine administration. Desipramine, the selective NA uptake inhibitor, blocked the effects of DSP4 upon amphetamine-induced rearing. NA depletion antagonised hyperactivity produced by the 2 mg/kg dose of amphetamine, but not the hyperactivity (rearing or locomotion) effects of amphetamine at 1, 4 or 8 mg/kg.

Key words

NA depletion d-Amphetamine DSP4 Neonatal 6-OHDA Adult 6-OHDA Dorsal mundle 6-OHDA DMI Hyperactivity Rearing Locomotion Dose Rat 

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References

  1. Archer T, Jonsson G, Ross SB (1984) A parametric study of the effects of the noradrenaline neurotoxin DSP4 on avoidance acquisition and noradrenaline neurones in the CNS of the rat. Br J Pharmacol 82:249–257Google Scholar
  2. Archer T, Ögren SO, Johansson G, Ross SB (1982) DSP-4-induced two-way active avoidance impairment in rats: Involvement of central and not peripheral noradrenaline depletion. Psychopharmacology 76:303–309Google Scholar
  3. Bickford PC, Mosimann WF, Hoffer BJ, Freedman R (1984) Effects of the selective noradrenergic neurotoxin DSP4 on cerebellar purkinje neuron electrophysiology. Life Sci 34:731–741Google Scholar
  4. Carlsson A (1970) Amphetamine and brain catecholamines. In: Costa E, Garattini S (eds) Amphetamines and related compounds. Raven Press: New York, pp 289–300Google Scholar
  5. Clark DWJ, Laverty R, Phelan EL (1972) Long-lasting peripheral and central effects of 6-hydroxydopamine in rats. Br J Pharmacol 44:233–243Google Scholar
  6. Corrodi H, Fuxe K, Ljungdahl Å, Ögren SO (1970) Studies on the action of some psychoactive drugs on central noradrenaline neurones after inhibition of dopamine-β-hydroxylase. Brain Res 24:451–470Google Scholar
  7. Creese I, Iversen SD (1975) The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res 83:242–248Google Scholar
  8. Everitt BJ, Robbins TW, Gaskin M, Fray PJ (1983) The effects of lesions to ascending noradrenergic neurons on discrimination learning and performance in the rat. Neurosci 2:397–410Google Scholar
  9. Jaim-Etcheverry G, Zieher LM (1980) DSP4: a novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res 188:513–523Google Scholar
  10. Jonsson J, Lewander T (1974) Effects of the dopamine-β-hydroxylase inhibitor FLA 63 on the kinetics of elimination of amphetamine in the rat. J Pharm Pharmacol 26:907–909Google Scholar
  11. Jonsson G, Sachs C (1976) Regional changes in [3H]-noradrenaline uptake, catecholamines and catecholamine synthetic and catabolic enzymes in rat brain following neonatal 6-hydroxydopamine treatment. Med Biol 54:286–297Google Scholar
  12. Jonsson G, Hallman H, Mefford I, Adams RN (1980). The use of liquid chromatography with electrochemical detection for the determination of adrenaline and other biogenic monoamines in the CNS. In: Fuxe K, Goldstein M, Hökfelt B, Hökfelt T (eds) Central adrenaline neurons. Pergamon Press: Oxford & New York, pp 59–71Google Scholar
  13. Jonsson G, Hallman H, Ponzio F, Ross S (1981) DSP4-(N-2-chloroethyl-N-ethyl-2-bromobenzylamine) — a useful denervation tool for central and peripheral noradrenaline neurons. Eur J Pharmacol 72:173–188Google Scholar
  14. Jonsson G, Pycock C, Fuxe K, Sachs C (1974) Changes in the development of central noradrenaline neurons following neonatal administration of 6-hydroxydopamine. J Neurochem 22:621–626Google Scholar
  15. Keller R, Oke A, Mefford I, Adams RN (1980) The use of liquid chromatographic analysis of catecholamines — routine assay for regional brain mapping. Life Sci 19:995–1004Google Scholar
  16. Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522Google Scholar
  17. Kirk RE (1968) Experimental Design: Procedures for the behavioral sciences. Brooks/Cole, Belmont CaliforniaGoogle Scholar
  18. König JFR, Klippel RA (1963) The rat brain: A stereotaxic atlas. Williams and Wilkins, BaltimoreGoogle Scholar
  19. Lewander T (1977) Effects of amphetamine in animals. In: Born GVR, Eichler O, Farah A, Herken H, Welch AD (eds) Handbook of experimental pharmacology. Springer-Verlag: Berlin, pp. 33–246Google Scholar
  20. Mason ST (1981) Noradrenaline in the brain: Progress in theories of behavioral function. Prog Neurobiol 16:263–303Google Scholar
  21. Mason ST, Iversen SD (1975) Learning in the absence of forebrain noradrenaline. Nature 258:422–424Google Scholar
  22. Mogilnicka E, Dooley DJ, Boissard CG, Delini-Stula A (1983) Altered hindlimb extension in the rat after DSP4: A useful marker of central noradrenergic depletion. Eur J Pharmacol 87:345–347Google Scholar
  23. Moore K (1978) Amphetamines: Biochemical and behavioural actions in animals. In Iversen LL, Iversen SD, Snyder SA (eds) Handbook of Psychopharmacology, Plenum Press, New York, pp 41–98Google Scholar
  24. Obianwu HO (1969) Possible functional differentiation between the stores from which adrenergic nerve stimulation, tyramine and amphetamine release noradrenaline. Acta Physiol Scand 75:92–101Google Scholar
  25. Ögren SO, Archer T, Johansson C (1983) Evidence for a selective brain noradrenergic involvement in the locomotor stimulant effects of amphetamine in the rat. Neurosci Lett 43:327–331Google Scholar
  26. Randrup A, Munkvad I (1965) Special antagonism of amphetamine-induced abnormal behaviour: Inhibition of stereotyped activity with increase of some normal activities. Psychopharmacologia 7:416–422Google Scholar
  27. Rolinski Z, Scheel-Krüger J (1973) The effect of dopamine and noradrenaline antagonists on amphetamine-induced locomotor activity in mice and rats. Acta Pharmacol Toxicol 33:385–399Google Scholar
  28. Ross SB (1976) Long term effect of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurons in the rat brain and heart. Br J Pharmacol 58:521–527Google Scholar
  29. Siegel S (1956) Nonparametric statistics for the behavioral sciences. McGraw-Hill, New YorkGoogle Scholar
  30. Snedecor GW, Cochran WG (1967) Statistical Methods. The Iowa State University Press: Ames, IowaGoogle Scholar
  31. Sulser F, Sanders-Bush E (1971) Effect of drugs on amines in the CNS. Ann Rev Pharmacol 11:209–230Google Scholar
  32. Svensson TH (1970) The effect of inhibition of catecholamine synthesis on dexamphetamine induced central stimulation. Eur J Pharmacol 12:161–166Google Scholar
  33. Thornburg JE, Moore KE (1973) The relative importance of dopaminergic and noradrenergic neuronal system for the stimulation of locomotor activity induced by amphetamine and other drugs. Neuropharmacology 12:853–866Google Scholar
  34. Von Voigtlander PF, Moore KE (1973) Involvement of nigro-striatal neurons in the in vivo release of dopamine by amphetamine, amantadine and tyramine. J Pharmacol Exp Ther 184:542–552Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Trevor Archer
    • 1
  • Anders Fredriksson
    • 2
  • Gösta Jonsson
    • 3
  • Tommy Lewander
    • 1
  • Abdul K. Mohammed
    • 2
  • Svante B. Ross
    • 1
  • Ulf Söderberg
    • 2
  1. 1.R & D LaboratoriesAstra Läkemedel ABSödertäljeSweden
  2. 2.Neurophysiology Laboratory and Psychiatric Research CenterUller»kers SjukhusUppsalaSweden
  3. 3.Dept. of HistologyKarolinska InstitutetStockholmSweden

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