Skip to main content
Log in

DSP4-induced two-way active avoidance impairment in rats: Involvement of central and not peripheral noradrenaline depletion

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) (50 mg/kg IP), a new selective noradrenaline (NA) neurotoxin, was found to cause a severe impairment of the acquisition of a two-way active avoidance task 1 week following adminsitration, an effect that was blocked by the selective NA uptake inhibitor desipramine. In a second experiment, systemically injected 6-OHDA (2×30 mg/kg IP) was not found to cause any avoidance impairment, althogh its effects upon peripheral NA were still evident 21 days after administration: The peripheral NA depletion caused by DSP4 almost disappeared 14 days after injection. In a third experiment, the avoidance impairment induced by DSP4 was produced even 10 weeks after treatment. Data from both the shuttlebox experiment and an activity box experiment suggest that the acquisition impairment is not readily explained on the basis of some deficit in spontaneous behavior or an altered perception of pain. The present data suggest that the effect of DSP4 upon active avoidance asquisition is mediated via central, and not peripheral NA neurons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Archer T (1982) DSP4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine), a new noradrenaline neurotoxin, and the stimulus conditions affecting aquisition of two-way active avoidance. J Comp Physiol Psychol (in press)

  • Archer T, Ögren SO, Ross SB (1981a) N-2-Chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4), a new selective noradrenaline neurotoxin, and taste neophobia in the rat. Physiol Psychol 9:197–202

    Google Scholar 

  • Archer T, Ögren SO, Ross SB, Johansson G (1981b) DSP4, a selective noradrenaline neurotoxin, and avoidance learning in the rat. In: Bradshaw CM, Szabadi E, Lowe CF (eds) Quantification of steadystate operant behaviour. Elsevier/North Holland Biomedical Press, Amsterdam, pp 445–448

    Google Scholar 

  • Atack C, Magnusson T (1978) A procedure for the isolation of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from the same tissue sample using a single column of strongly acidic cation exchange resin. Acta Pharmacol Toxicol (Copenh) 42:35–57

    Google Scholar 

  • Beninger RJ, Mason ST, Phillips AG, Fibiger HC (1980a) The use of conditioned suppression to evaluate the nature of neuroleptic-induced avoidance deficits. J Pharmacol Exp Ther 213:623–627

    Google Scholar 

  • Beninger RJ, Mason ST, Phillips AG, Fibiger HC (1980b) The use of extinction to investigate the nature of neuroleptic-induced avoidance deficits. Psychopharmacology 69:11–18

    Google Scholar 

  • Callingham BA (1966) The effects of imipramine and related compounds on the uptake of noradrenaline into sympathetic nerve endings. In: GArattini S (ed) Proceedings of the First International Symposium on Antidepressant Drugs. Excerpta Medica, Amsterdam, pp 34–43

    Google Scholar 

  • Carlsson A, Lindqvist M (1973) Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J Pharm Pharmacol 25:437–440

    Google Scholar 

  • D'Amour FE, Smith DL (1941) A method for determining loss of pain sensation. J Pharmacol Exp Ther 71:74–79

    Google Scholar 

  • Eddy NB, Leimbach D (1953) Synthetic analgesics. II. Dithienylbutenyland ditheinylbutelamines. J Pharmacol Exp Ther 107:385–393

    Google Scholar 

  • Fibiger HC, Mason ST (1978) The effects of dorsal bundle injections of 6-hydroxydopamine on avoidance responding in rats. Br J Pharmacol 64:601–605

    Google Scholar 

  • Huang YH, Redmond DE, Snyder DR, Maas JW (1975) In vivo location and destruction of the locus coeruleus in the stumptail macague (Macaca arctoides). Brain Res 100:157–162

    Google Scholar 

  • Jaim-Etcheverry G, Zieher LM (1980) DSP4: A novel compound with eneurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res 188:513–523

    Google Scholar 

  • Jonsson G, Hallman H, Ponzio F, Ross S (1981) DSP4-(N-2-chloroethyl-N-ethy-2-bromobenzylamine): A useful denervation tool for central and peripheral noradrenaline neurons. Eur J Pharmacol 72:173–188

    Google Scholar 

  • Kirk RE (1968) Experimental design: Procedures for the behavioral sciences. Brooks Cole, Belmont CA

    Google Scholar 

  • Mason ST, Fibiger HC (1979) Noradrenaline and avoidance learning in the rat. Brain Res 161:321–334

    Google Scholar 

  • Mason ST, Iversen SD (1977) Behavioral basis of the dorsal bundle extinction effect. Pharmacol Biochem Behav 7:373–379

    Google Scholar 

  • Mason ST, Iversen SD (1979) Theories of the dorsal bundle extinction effect. Brain Res Rev 1:107–137

    Google Scholar 

  • Oei TPS, King MG (1980) Catecholamines and aversive learning: A review. Neurosci Biobehav Rev 4:161–173

    Google Scholar 

  • Ögren SO, Fuxe K (1974) Learning, brain noradrenaline and the pituitary-adrenal axis. Med Biol 52:399–405

    Google Scholar 

  • Ögren SO, Fuxe K (1977) On the role of noradrenaline and the pituitary-adrenal axis in avoidance learning. Studies with corticosterone. Neurosci Lett 5:291–296

    Google Scholar 

  • Ögren SO, Holm AC (1980) Test-specific effects of the 5-HT reuptake inhibitors alaproclate and zimelidine on pain sensitivity and morphine analgesia. J Neural Trans 47:253–271

    Google Scholar 

  • Ögren SO, Archer T, Ross SB (1980) Evidence for a role of the locus coeruleus noradrenaline system in learning. Neurosci Lett 20:351–356

    Google Scholar 

  • Ögren SO, Archer T, Fuxe K, Eneroth P (1981) Glucocorticoids, catecholamines and avoidance learning. In: Fuxe K, Gustafsson JA, Wetterberg L (eds) Symposium on steroid hormone regulation of the brain. Pergamon, Oxford New York, pp 355–377

    Google Scholar 

  • 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

    Google Scholar 

  • Ross SB, Renyi AL (1976a) On the long-lasting inhibitory effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on the active uptake of noradranaline. J Pharm Pharmacol 28:458–459

    Google Scholar 

  • Ross SB, Renyi AL (1976b) Structural requirements for inhibition of the uptake of noradrenaline and 5-hydroxytryptamine by tricyclic antidepressant and related compounds. In: Knoll J, Magyar K (eds) Symposium on pharmacology of catecholaminergic and serotonergic mechanisms. Akadémiai Kiado, Budapest, pp 1–8

    Google Scholar 

  • Ross SB, Renyi AL, Ögren SO (1972) Inhibition of the uptake of noradrenaline and 5-hydroxytryptamine by chlorphentermine and chlorimipramine. Eur J Pharmacol 17:107–112

    Google Scholar 

  • Ungerstedt U (1971) Stereotoxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand (Suppl) 367:1–48

    Google Scholar 

  • Zieher LM, Jaim-Etcheverry G (1980) Neurotoxicity of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) on noradrenergic neurons is mimicked by its cyclic aziridinium derivative. Eur J Pharmacol 65:249–256

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Archer, T., Ögren, S.O., Johansson, G. et al. DSP4-induced two-way active avoidance impairment in rats: Involvement of central and not peripheral noradrenaline depletion. Psychopharmacology 76, 303–309 (1982). https://doi.org/10.1007/BF00449115

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00449115

Key words

Navigation