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Retarded acquisition of a temporal discrimination following destruction of noradrenergic neurones by systemic treatment with DSP4

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Abstract

This experiment examined the effect of destroying central noradrenergic neurones, using the selective neurotoxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) on the acquisition and performance of discrimination between two time intervals. Rats that had received systemic treatment with DSP4 and vehicle-treated control rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus and lever B following an 8-s presentation of the same stimulus. Both groups acquired the discrimination (>90% correct choices) within 15 sessions; however, the DSP4-treated group showed significantly slower acquisition than the control group. When stable performance had been attained, ‘probe’ trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. Neither the bisection point (duration corresponding to 50% choice of lever B) nor the Weber fraction differed significantly between the DSP4-treated and control groups. The levels of noradrenaline were markedly reduced in the neocortex and hippocampus of the DSP4-treated group, but the levels of dopamine and 5-hydroxytryptamine were not altered. The results indicate that noradrenaline depletion induced by DSP4 retarded the acquisition of temporal discrimination, but did not impair steady-state discriminative precision.

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References

  • Archer T (1982) The role of noradrenaline in learned behaviors: studies using DSP4. Scand J Psychol Suppl 1:61–71

    Google Scholar 

  • Archer T, Mohammed AK, Ross SB, Soderberg U (1983) T-maze learning, spontaneous activity and food intake recovery following systemic administration of noradrenaline neurotoxin DSP4. Pharmacol Biochem Behav 19:121–130

    Google Scholar 

  • Bradshaw CM, Szabadi E (1989) Central neurotransmitter systems and the control of operant behaviour by ‘natural’ positive reinforcers. In: Liebman JM, Cooper SJ (es) The neuropharmacological basis of reward. Oxford University Press, Oxford, pp 320–376

    Google Scholar 

  • Brodie BB, Shore PA (1957) A concept for a role of serotonin and norepinephrine as chemical mediators in the brain. Ann NY Acad Sci 66:631–642

    Google Scholar 

  • Clement HW, Gemsa D, Wesemann W (1992) Serotonin-norepinephrine interactions: a voltammetric study on the effect of serotonin receptor stimulation followed in the N. raphe dorsalis and locus coeruleus. J Neural Transm 88:11–23

    Google Scholar 

  • Church RM, Deluty MZ (1977) Bisection of temporal intervals. J Exp Psychol [Anim Behav Proc] 3:216–228

    Google Scholar 

  • Crow TJ, Deakin JFW (1985) The neurochemistry of behaviour, the pharmacology of centrally acting drugs and the mechanism of the disturbance in psychiatric disease. In: Shephard M, Zangwill OL (eds) Handbook of psychiatry, vol 5. Cambridge University Press, Cambridge, pp 137–182

    Google Scholar 

  • 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. Neurocience 10:397–410

    Google Scholar 

  • Fetterman JG, Killeen PR (1992) Time discrimination in Columba livia and Homo sapiens. J Exp Psychol [Anim Behav Proc] 18:80–94

    Google Scholar 

  • Gorea E, Adrien J (1988) Serotonergic regulation of noradrenergic coerulean neurons: electrophysiological evidence for the involvement of 5-HT2 receptors. Eur J Pharmacol 154:285–291

    Google Scholar 

  • Graham S, Ho M-Y, Bradshaw CM, Szabadi E (1994) Facilitated acquisition of a temporal discrimination following destruction of the ascending 5-hydroxytryptaminergic pathways. Psychopharmacology 116:373–378

    Google Scholar 

  • Gray JA (1982) The neuropsychology of anxiety: an enquiry into the functions of septo-hippocampal system. Oxford University Press, Oxford

    Google Scholar 

  • Heffner TG, Hartman JA, Seiden LS (1980) A method for the regional dissection of the rat brain. Pharmacol Biochem Behav 13:453–456

    Google Scholar 

  • Jonsson G, Hallman H, Ponzio F, Ross SB (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

    Google Scholar 

  • Jonsson G, Hallman H, Sundstrom E (1982) Effect of the noradrenaline neurotoxin DSP4 on the postnatal development of central noradrenaline neurons in the rat. Neuroscience 7:2895–2907

    Google Scholar 

  • Killeen PR, Fetterman JG (1988) A behavioral theory of timing. Psychol Rev 95:274–295

    Google Scholar 

  • Leger L, Descarries L (1978) Serotonin nerve terminals in the locus coeruleus of adult rat: a radiographic study. Brain Res 145:1–13

    Google Scholar 

  • Lewis D (1960) Quantitative methods in psychology. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Mason ST (1984) Catecholamines and behaviour. Cambridge University Press, Cambridge

    Google Scholar 

  • Mason ST, Lin D (1980) Noradrenaline and selective attention in the rat. J Com Physiol Psychol 94:819–832

    Google Scholar 

  • McRae-Degueurce A, Dennis T, Leger L, Scatton B (1985) Regulation of noradrenergic neuronal activity in the locus coeruleus by serotonergic afferents. Physiol Psychol 13:188–196

    Google Scholar 

  • Morley MJ, Bradshaw CM, Szabadi E (1987) DSP4 alters the effect ofd-amphetamine on variable-interval performance: analysis in terms of Herrstein's equation. Psychopharmacology 92:247–253

    Google Scholar 

  • Morley MJ, Shah K, Bradshaw CM, Szabadi E (1988) DSP4 and Herrstein's equation: further evidence for a role of noradrenaline in the maintenance of operant behaviour by positive reinforcement. Psychopharmacology 96:551–556

    Google Scholar 

  • Morrissey G, Wogar MA, Bradshaw CM, Szabadi E (1993) Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on timing behaviour investigated with an interval bisection task. Psychopharmacology 112:80–85

    Google Scholar 

  • Normile HJ, Altman HJ (1987) Evidence for a possible interaction between noradrenergic and serotonergic neurotransmission in the retrieval of a previously learned aversive habit in mice. Psychopharmacology 92:388–392

    Google Scholar 

  • Ogren S-O (1985) Central serotonin neurones in avoidance learning: interactions with noradrenaline and dopamine neurones. Pharmacol Biochem Behav 23:107–123

    Google Scholar 

  • Platt JR, Davis ER (1983) Bisection of temporal intervals by pigeons. J Exp Psychol [Anim Behav Proc] 9:160–170

    Google Scholar 

  • Robbins TW (1984) Cortical noradrenaline, attention and arousal. Psychol Med 14:13–21

    Google Scholar 

  • Robbins TW, Everitt BJ, Cole BJ, Archer T, Mohammed A (1985) Functional hypotheses of the coeruleocortical noradrenergic projection: a review of recent experimentation and theory. Physiol Psychol 13:127–150

    Google Scholar 

  • Tanii H, Huang J, Hashimoto K (1993) Involvement of noradrenergic and 5-hydroxytryptaminergic systems in allylnitrileinduced head twitching. Brain Res 626:265–271

    Google Scholar 

  • Wogar MA, Bradshaw CM, Szabadi E (1991) Evidence for an involvement of 5-hydroxytryptaminergic neurones in the maintenance of operant behaviour by positive reinforcement. Psychopharmacology 105:119–124

    Google Scholar 

  • Wogar MA, Bradshaw CM, Szabadi E (1992) Impaired acquisiton of temporal differentiation performance following lesions of the ascending 5-hydroxytryptaminergic pathways. Psychopharmacology 107:373–378

    Google Scholar 

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Ho, M.Y., Velazquez Martinez, D.N., Cabrera, M.L. et al. Retarded acquisition of a temporal discrimination following destruction of noradrenergic neurones by systemic treatment with DSP4. Psychopharmacology 118, 332–337 (1995). https://doi.org/10.1007/BF02245963

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  • DOI: https://doi.org/10.1007/BF02245963

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