Skip to main content
Log in

Operant behavioural and neurochemical effects after neonatal 6-hydroxydopamine treatment

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

Abstract

Newborn rats were treated at 1 and 2 days after birth with 100 mg/kg 6-hydroxydopamine (6OHDA), s.c. Testing on several operant behavioural tasks was begun at 6 months of age. On a fixed ratio 30 (FR 30) schedule of food reinforcement, the neonatal 6OHDA treated rats responded at a significantly higher rate. Further analysis of the FR 30 response pattern indicated that the higher rate was due to a decrease in the amount of time spent pausing after the receipt of each reinforcer. The 6OHDA treatment failed to alter the rat's behaviour during the extinction of the FR 30 response and on the progressive ratio or variable interval schedules of food reinforcement. Biochemical analysis of several brain areas at 9 months of age showed a decrease in noradrenaline (NA) levels in the cerebral cortex and hippocampus, while in the pons-medulla NA, content was doubled. The tyrosine hydroxylase activity in these same brain areas was not significantly altered, but there appeared to be some decrease in the activity of this enzyme in the hippocampus. Comparison of the operant behavioural effects seen after various lesioning procedures in this and other studies, suggest the effects on FR performance are a result of destruction of NA neurons in the hippocampus and/or the apparent regeneration of neurons in the pons-medulla.

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

  • Grey, J. A., Ball, G. G.: Frequency-specific relation between hippocampal theta rhythm, behavior and amobarbital action. Science168, 1246–1248 (1970)

    Google Scholar 

  • Hendry, I. A., Iversen, L. L.: Effect of nerve growth factor and its antiserum on tyrosine hydroxylase activity in mouse superior cervical sympathetic ganglia. Brain Res.29, 159–162 (1971)

    Google Scholar 

  • Jonsson, G., Pycock, Ch., Fuxe, K., Sachs, C.: Changes in the development of central noradrenaline neurons following neonatal administration of 6-hydroxydopamine. J. Neurochem.,22, 419–426 (1974)

    Google Scholar 

  • Karki, N., Kuntzman, R., Brodie, B. B.: Storage, synthesis and metabolism of monoamines in the developing brain. J. Neurochem.9, 53–58 (1962)

    Google Scholar 

  • Kimble, D. P.: Possible inhibitory function of the hippocampus. Neuropsychologia7, 235–244 (1969)

    Google Scholar 

  • Laverty, R., Liew, M.-C., Taylor, K. M.: Selective depletion of brain regional noradrenaline by systemic 6-hydroxydopamine in newborn rats. In: Frontiers in catecholamine research, E. Usdin and S. Snyder, eds, pp. 1063–1065. Oxford: Pergamon Press 1973

    Google Scholar 

  • Laverty, R., Taylor, K. M.: The fluorimetric assay of catecholamines and related compounds. Analyt. Biochem.22, 269–279 (1968)

    Google Scholar 

  • Liew, M.-C., Laverty, R.: Mechanism of selective depletion of brain regional noradrenaline by systemic 6-hydroxydopamine in newborn rats. Europ. J. Pharmacol.33, 165–172 (1975)

    Google Scholar 

  • Loizou, L. A.: The postnatal ontogeny, of monoamine-containing neurons in the central nervous system of the albino rat. Brain Res.40, 395–418 (1972)

    Google Scholar 

  • Mason, S. T., Iversen, S. D.: Learning in the absence of forebrain noradrenaline. Nature (Lond.)258, 422–424 (1975)

    Google Scholar 

  • McGeer, E. G., Gibson, S., McGeer, P. L.: Some characteristics of brain tyrosine hydroxylase. Canad. J. Biochem.75, 1557–1563 (1967)

    Google Scholar 

  • Pappas, B. A., Peters, D. A. U., Sobrian, S. K., Blouin, A., Drew, B.: Early behavioral and catecholaminergic effects of 6-hydroxydopamine and guanethidine in the neonatal rat. Pharmacol. Biochem. Behav.3, 681–685 (1975)

    Google Scholar 

  • Pappas, B. A., Sobrian, S. K.: Neonatal sympathectomy by 6-hydroxydopamine in the rat: No effect on behavior, but changes in endogenous brain norepinephrine. Life Sci.11, 653–659 (1972)

    Google Scholar 

  • Peterson, D. W., Sparber, S. B.: Increased fixed-ratio performance and differential, d-and l-amphetamine action following norepinephrine depletion by intraventricular 6-hydroxydopamine. J. Pharmacol. exp. Ther.191, 349–357 (1974)

    Google Scholar 

  • Saari, M., Pappas, B. A.: Neonatal 6-hydroxydopamine sympathectomy reduces foot shock-induced suppression of water-licking in normotensive and, hypertension rats. Nature New Biol.244, 181–183 (1973)

    Google Scholar 

  • Sachs, Ch.: Development of the blood-brain barrier, for 6-hydroxydopamine. J. Neurochem.20, 1753–1760 (1973)

    Google Scholar 

  • Sachs, Ch., Jonsson, G.: Effects of 6-hydroxydopamine on central noradrenaline neurons during ontogeny. Brain Res99, 277–291 (1975)

    Google Scholar 

  • Schoenfeld, R. I., Uretsky, N. J.: Operant behaviour and catecholamine-containing neurons: Prolonged increase in lever pressing after 6-hydroxydopamine. Europ. J. Pharmacol.20, 351–362 (1972)

    Google Scholar 

  • Schoenfeld, R. I., Zigmond, M. J.: Behavioural pharmacology of 6-hydroxydopamine. In: Frontiers in Catecholamine Research, E. Usdin, and S. Snyder, eds., pp. 695–700. New York-Toronto-Oxford-Sydney-Braunschweig. Pergamon Press 1973

    Google Scholar 

  • Singh, B., De Champlain, J.: Altered ontogenesis of central norepinephrine neurons following neonatal treatment with 6-hydroxydopamine. Brain Res.48, 432–437 (1972)

    Google Scholar 

  • Taylor, K. M., Clark, D. W. J., Laverty, R., Phelan, E. L.: Specific noradrenergic neurons destroyed by 6-hydroxydopamine injected into newborn rats. Nature New Biol.239, 247–248 (1972)

    Google Scholar 

  • Thornton, E. W., Goudie, A. J., Bithell, V.: The effects of neonatal 6-hydroxydopamine induced sympathectomy on response inhibition in extinction. Life Sci.17, 363–368 (1975)

    Google Scholar 

  • Versteeg, D. H. G., Van Ree, J. M., Provost, A. P., De Jong, W.: Neonatal 6-hydroxydopamine treatment: Noradrenaline levels and in vitro3H-catecholamine synthesis in descrete brain regions of adult rats. Life Sci.15, 2127–2134 (1974)

    Google Scholar 

  • Weiss, B., Gott, C. T.: A microanalysis of drug effects on fixedratio performance in pigeons. J Pharmacol. exp. Ther.180, 189–202 (1972)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peterson, D.W., Laverty, R. Operant behavioural and neurochemical effects after neonatal 6-hydroxydopamine treatment. Psychopharmacology 50, 55–60 (1976). https://doi.org/10.1007/BF00634155

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00634155

Key words

Navigation