Abstract
A series of experiments examined the effects of lesions of the dorsal noradrenergic bundle (DNAB), induced by 6-hydroxydopamine (6-OHDA), on the behavioural response to systemic and intra-accumbens amphetamine, using a rat analogue of Leonard's 5-choice serial reaction time task for humans. Although the 6-OHDA DNAB lesion produced a profound depletion of cortical noradrenaline (NA) (to around 5% of control levels) it did not impair any aspect of performance on this task. Both systemic and intra-accumbens amphetamine increased behavioural measures of impulsivity of responding, but neither impaired discriminative accuracy in the sham-operated control rats. However, the DNAB lesioned rats did show a discriminative impairment following both low doses of systemic amphetamine, and intra-accumbens amphetamine. The latter effect was antagonised by systemic administration of the specific dopaminergic (DA) antagonist alpha-flupenthixol. The DNAB lesion did not alter the effect of amphetamine on any other behavioural measure, including speed and impulsivity of responding. These results suggest that although DA and NA participate in qualitatively different behavioural processes, the effects of DNAB lesions on attentional processes depend on the level of DA activity within the nucleus accumbens.
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References
Acheson A, Zigmond MJ, Stricker EM (1980) Compensatory increases in tyrosine hydroxylase activity in rat brain after intraventricular injections of 6-hydroxydopamine. Science 207:537–540
Antelman SM, Caggiula AR (1977) Norepinephrine-dopamine interactions and behaviour. Science 195:646–653
Archer T, Fredriksson A, Jonsson G, Lewander T, Mohammed A, Ross S, Soderberg U (1986) Central noradrenaline depletion antagonises aspects of d-amphetamine induced hyperactivity in the rat. Psychopharmacology 88:141–146
Braestrup C (1977) Changes in drug-induced stereotyped behavior after 6-OHDA lesions in noradrenaline neurons. Psychopharmacology 51:199–204
Bruto V, Beauchamp C, Zacharko R, Anisman H (1984) Amphetamine-induced perseverative behavior in a radial arm maze following DSP-4 or 6-OHDA pretreatment. Psychopharmacology 83:62–69
Carli M, Robbins TW, Evenden JL, Everitt BJ (1983) Effects of lesions to ascending noradrenergic neurons on performance of a 5-choice serial reaction time task in rats: Implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal. Behav Brain Res 9:361–380
Creese I, Iversen SD (1975) The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res 83:419–436
Dalton JCH, Roberts DCS, McIntyre DC (1985) Supersensitivity to the anticonvulsant and proconvulsant activity of clonidine following noradrenaline depletion induced by 6-hydroxydopamine. Psychopharmacology 85:319–322
Engberg G, Svensson TH (1979) Amphetamine induced inhibition of central noradrenergic neurons: A pharmacological analysis. Life Sci 24:2245–2253
Groves PM, Tepper JM (1983) Neural mechanisms of action of amphetamine. In: Creese I (ed) Stimulants: neurochemical, behavioural and clinical perspectives. Raven, New York, pp 81–129
Harik SI, Duckrow RB, La Manna JC, Rosenthal M, Sharma VK, Bannerjee SP (1981) Cerebral compensation for chronic noradrenergic denervation induced by locus coeruleus lesions: Recovery of receptor binding, isoproternol-induced adenylate cyclase activity and oxidative metabolism. J Neurosci 1:641–649
Huang YH, Maas JW (1981) d-Amphetamine at low doses suppresses noradrenergic function. Eur J Pharmacol 75:187–195
Iversen LL (1985) Mechanisms of action of antipsychotic drugs: Retrospect and prospect. In: Iversen SD (ed) Psychopharmacology: recent advances and future prospect. Oxford University Press, Oxford, pp 204–215
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
Koek W, Slangen JL (1983) Effects of amphetamine and morphine on discrimination: Signal detection analysis and assessment of response repetition in the performance deficit. Psychopharmacology 80:125–128
Kostowski W, Jerlicz M, Bidzinski A, Hauptman H (1977) Behavioral effects of neuroleptics, apomorphine and amphetamine after bilateral lesions of the locus coeruleus in rats. Pharmacol Biochem Behav 7:289–293
Ksir C, Slifer B (1982) Drug discrimination performance at two levels of stimulus control. Psychopharmacology 76:286–290
Lyon M, Robbins TW (1975) The action of central nervous system stimulant drugs: A general theory concerning amphetamine effects. Curr Dev Psychopharmacol 2:79–163
Mason ST, Iversen SD (1979) Theories of the dorsal bundle extinction effect. Brain Res Rev 1:107–137
Mefford I (1981) Application of high performance liquid chromatography with electrochemical detection to neurochemical analysis; measurement of catecholamines, serotonin and metabolites in the rat brain. J Neurochem Meth 3:207–224
Ogren 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
Pellegrino LJ, Cushman AJ (1967) A stereotaxic atlas of the rat brain. Appleton-Century-Crofts, New York
Pisa M, Fibiger HC (1983) Intact selective attention in rats with lesions of the dorsal noradrenergic bundle. Behav Neurosci 97:519–529
Robbins TW, Everitt BJ (1982) Functional studies of the central catecholamines. Int Rev Neurobiol 23:303–365
Robbins TW, Sahakian BJ (1983) Behavioral effects of psychomotor stimulant drugs: Clinical and neuropsychological implications. In: Creese I (ed) Stimulants: neurochemical, behavioral and clinical perspectives. Raven, New York, pp 301–338
Robbins TW, Roberts DCS, Koob GF (1983) Effects of d-amphetamine and apomorphine upon operant behavior and schedule-induced licking in rats with 6-hydroxydopamine-induced lesions of the nucleus accumbens. J Pharmacol Exp Ther 224:662–673
Roberts DCS, Zis AP, Fibiger HC (1975) Ascending catecholamine pathways and amphetamine-induced locomotor activity: Importance of dopamine and apparent non-involvement of norepinephrine. Brain Res 93:441–454
U'Prichard DC, Reisine TD, Mason ST, Fibiger HC, Yamamura HI (1980) Modulation of rat brain alpha- and beta-adrenergic receptor populations by lesions of the dorsal noradrenergic bundle. Brain Res 187:143–154
Weight ML, Ridley RM, Baker HF (1980) The effects of amphetamine on delayed response performance in the monkey. Pharmacol Biochem Behav 12:861–864
Wolf G (1971) Elementary histology for neuropsychologists. In: Myers RD (ed) Methods in psychobiology, vol 1. Academic Press, London New York, pp 281–300
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Cole, B.J., Robbins, T.W. Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: New evidence for central dopaminergic-noradrenergic interactions. Psychopharmacology 91, 458–466 (1987). https://doi.org/10.1007/BF00216011
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DOI: https://doi.org/10.1007/BF00216011