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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
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 82:249–257
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 76:303–309
Bickford PC, Mosimann WF, Hoffer BJ, Freedman R (1984) Effects of the selective noradrenergic neurotoxin DSP4 on cerebellar purkinje neuron electrophysiology. Life Sci 34:731–741
Carlsson A (1970) Amphetamine and brain catecholamines. In: Costa E, Garattini S (eds) Amphetamines and related compounds. Raven Press: New York, pp 289–300
Clark DWJ, Laverty R, Phelan EL (1972) Long-lasting peripheral and central effects of 6-hydroxydopamine in rats. Br J Pharmacol 44:233–243
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 24:451–470
Creese I, Iversen SD (1975) The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res 83:242–248
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 2:397–410
Jaim-Etcheverry G, Zieher LM (1980) DSP4: a novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res 188:513–523
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 26:907–909
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 54:286–297
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 59–71
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 72:173–188
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 22:621–626
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 19:995–1004
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 94:507–522
Kirk RE (1968) Experimental Design: Procedures for the behavioral sciences. Brooks/Cole, Belmont California
König JFR, Klippel RA (1963) The rat brain: A stereotaxic atlas. Williams and Wilkins, Baltimore
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. 33–246
Mason ST (1981) Noradrenaline in the brain: Progress in theories of behavioral function. Prog Neurobiol 16:263–303
Mason ST, Iversen SD (1975) Learning in the absence of forebrain noradrenaline. Nature 258:422–424
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 87:345–347
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 41–98
Obianwu HO (1969) Possible functional differentiation between the stores from which adrenergic nerve stimulation, tyramine and amphetamine release noradrenaline. Acta Physiol Scand 75:92–101
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 43:327–331
Randrup A, Munkvad I (1965) Special antagonism of amphetamine-induced abnormal behaviour: Inhibition of stereotyped activity with increase of some normal activities. Psychopharmacologia 7:416–422
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 33:385–399
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 58:521–527
Siegel S (1956) Nonparametric statistics for the behavioral sciences. McGraw-Hill, New York
Snedecor GW, Cochran WG (1967) Statistical Methods. The Iowa State University Press: Ames, Iowa
Sulser F, Sanders-Bush E (1971) Effect of drugs on amines in the CNS. Ann Rev Pharmacol 11:209–230
Svensson TH (1970) The effect of inhibition of catecholamine synthesis on dexamphetamine induced central stimulation. Eur J Pharmacol 12:161–166
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 12:853–866
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 184:542–552
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Archer, T., Fredriksson, A., Jonsson, G. et al. Central noradrenaline depletion antagonizes aspects ofd-amphetamine-induced hyperactivity in the rat. Psychopharmacologia 88, 141–146 (1986). https://doi.org/10.1007/BF00652230
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00652230