title: Life-spanning behavioural and adrenal dysfunction induced by prenatal hypoxia in the rat is prevented by the calcium antagonist nimodipine.
abstract: 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.
authors.affiliation: Central Research Laboratory, Postgraduate Medical University, Budapest, Hungary.
authors.forename: C
authors.initials: C
authors.lastname: Nyakas
authors.forename: B
authors.initials: B
authors.lastname: Buwalda
authors.forename: E
authors.initials: E
authors.lastname: Markel
authors.forename: S M
authors.initials: SM
authors.lastname: Korte
authors.forename: P G
authors.initials: PG
authors.lastname: Luiten
mesh_terms: D000309:Adrenal Insufficiency / Q000209:etiology / Q000517:prevention & control*; D000375:Aging / Q000502:physiology; D000740:Anemia / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control*; D003345:Corticosterone / Q000097:blood; D004193:Discrimination Learning / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005311:Fetal Hypoxia / Q000188:drug therapy*; D008708:Methemoglobinemia / Q000503:physiopathology; D009553:Nimodipine / Q000494:pharmacology*; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000503:physiopathology; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012919:Social Behavior; D013312:Stress, Physiological / Q000503:physiopathology; D014828:Vocalization, Animal / Q000187:drug effects
chemical_list: D009553:Nimodipine; D003345:Corticosterone