Life‐spanning Behavioural and Adrenal Dysfunction Induced by Prenatal Hypoxia in the Rat is Prevented by the Calcium Antagonist Nimodipine

Csaba Nyakas, Bauke Buwalda, Éva Markel, S. Mechiel Korte, Paul G.M. Luiten

Research output: Contribution to journalArticle

27 Citations (Scopus)


The long‐term behavioural effects of prenatal chronic anaemic hypoxia were investigated in young (5 months old), late adult (19 months) and aged Wistar rats (23–26 months). Sodium nitrite (2 g/l) offered in the drinking water during the second half of pregnancy served to evoke prenatal hypoxia. In parallel to nitrite treatment the Ca2+ channel blocker nimodipine (10 mg/kg) or vehicle alone was administered intragastrically once daily. Open‐field activity, intermale social behaviour, learning ability in a black–white discrimination paradigm and fear‐induced emotionality were assessed at different ages. Plasma corticosterone response to novelty stress was measured by blood sampling through chronic venous canulas at the age of 28 months. The nitrite‐exposed 5‐month‐old offspring started exploration in a novel open‐field with considerable delay. This delayed start‐latency was augmented in 19‐ and 23‐month‐old rats, pointing to exaggerated suppression of behavioural arousal. Nitrite‐induced hypoxia decreased the duration of social interactions during ageing. Aged rats exposed to nitrite were unable to learn a black–white discrimination but showed a normal generalized conditioned fear response (immobility) to the test situation as a whole. The conditioned fear‐induced vocalization was more frequent among hypoxic aged animals. The aged hypoxic rats displayed a prolonged plasma corticosterone stress response and had higher adrenal weight than their controls. The abnormal open‐field, social, learning and emotional behaviours, as well as the altered plasma corticosterone response, were prevented by prenatal nimodipine treatment.

Original languageEnglish
Pages (from-to)746-753
Number of pages8
JournalEuropean Journal of Neuroscience
Issue number5
Publication statusPublished - May 1994


  • ageing
  • brain damage
  • corticosterone
  • development
  • learning

ASJC Scopus subject areas

  • Neuroscience(all)

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