LIFE-SPANNING BEHAVIORAL AND ADRENAL DYSFUNCTION INDUCED BY PRENATAL HYPOXIA IN THE RAT IS PREVENTED BY THE CALCIUM-ANTAGONIST NIMODIPINE

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 t he drinking water during the second half of pregnancy served to evoke prenatal hypoxia. In parallel to nitrite treatment the Ca2+ channel bl ocker nimodipine (10 mg/kg) or vehicle alone was administered intragas trically once daily. Open-field activity, intermale social behaviour, learning ability in a black-white discrimination paradigm and fear-ind uced emotionality were assessed at different ages. Plasma corticostero ne response to novelty stress was measured by blood sampling through c hronic venous canulas at the age of 28 months. The nitrite-exposed 5-m onth-old offspring started exploration in a novel open-field with cons iderable delay. This delayed start-latency was augmented in 19- and 23 -month-old rats, pointing to exaggerated suppression of behavioural ar ousal. Nitrite-induced hypoxia decreased the duration of social intera ctions during ageing. Aged rats exposed to nitrite were unable to lear n a black-white discrimination but showed a normal generalized conditi oned 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 corti costerone stress response and had higher adrenal weight than their con trols. The abnormal open-field, social, learning and emotional behavio urs, as well as the altered plasma corticosterone response, were preve nted by prenatal nimodipine treatment.