Neonatal 6-hydroxydopa, but not DSP-4, elevates brainstem monoamines and impairs inhibitory avoidance learning in developing rats

Catherine A. Cornwell-Jones, Michael W. Decker, Julia W. Chang, Barry Cole, Kimberly M. Goltz, Thuy Tran, James L. McGaugh

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The involvement of brain monoamines in learning and memory in developing rats was studied by comparing the effects of 3 different noradrenergic neurotoxin treatments. Two experimental groups of male Sprague-Dawley rat pups were injected systemically with 50 μg/g of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) either on the day of birth or on postnatal days 17-18. Rats in the third experimental group were injected systemically with 60 μg/g of 6-hydroxydopa (6-OHDOPA) on postnatal days 0 and 2. Control littermates received vehicle. The animals were trained on an inhibitory avoidance task on postnatal days 27-29 and tested for retention 24 h later. The drug treatments produced comparable depletion of norepinephrine in the hippocampus and frontal cortex. 6-OHDOPA, but neither DSP-4 treatment, significantly elevated brainstem concentrations of norepinephrine and serotonin. In addition, 6-OHDOPA, but not DSP-4, significantly impaired retention of the inhibitory avoidance task. The impairment did not reflect insensitivity to the footshock used in training: both neonatal drug treatments tended to lower, not raise, footshock thresholds, as measured by a flinh test. High affinity choline uptake was not affected by either neonatal drug treatment in any of the brain areas examined. Thus, the 6-OHDOPA-induced behavioral deficit did not involve altered acetylcholine function. The results implicate brainstem monoamines in the modulation of learning and memory during development.

Original languageEnglish (US)
Pages (from-to)258-268
Number of pages11
JournalBrain Research
Volume493
Issue number2
DOIs
StatePublished - Jul 31 1989
Externally publishedYes

Keywords

  • 6-Hydroxydopa
  • Brainstem noradrenaline
  • Brainstem serotonin
  • Inhibiyory avoidance learning
  • N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine
  • Neonatal neurotoxin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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