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Altered catecholaminergic behavioral and hormonal responses in rats following early postnatal hypoxia
1Department of Physiology, School of Medicine, Loma Linda University, CA 92350.
Insights
Early life hypoxia in rats alters dopamine system development, affecting behavior and stress responses. These changes impact grooming, rearing, and stereotypy, with lasting effects on catecholaminergic pathways.
Area of Science:
- Neuroscience
- Developmental Biology
- Behavioral Science
Background:
- Prenatal hypoxia can impact behavioral functions and the development of the catecholaminergic neurotransmitter system.
- Postnatal stress can influence adult hypothalamic-pituitary-adrenal responsiveness.
- Dopaminergic/adrenergic agonists/antagonists can reveal subtle changes not evident in standard tests.
Purpose of the Study:
- To investigate the hypothesis that early postnatal hypoxia affects catecholamine system development.
- To determine if hypoxia-induced alterations in the catecholaminergic system lead to functional outcomes.
- To examine behavioral and endocrine responses following drug challenges in hypoxic rats.
Main Methods:
- Sprague-Dawley rats were exposed to hypoxia (10.5% O2) for 6 hours daily from postnatal day 2 to 10.
- Control litters received standard conditions.
- Behavioral tests, including open-field activity with apomorphine and haloperidol challenges, were conducted at various ages.
Main Results:
- Hypoxic animals exhibited significantly decreased body weights from postnatal day 10 to 100.
- Grooming activity was reduced, while rearing activity increased in hypoxic rats at postnatal day 21.
- Apomorphine-induced stereotypy was elevated in hypoxic rats at postnatal day 39.
Conclusions:
- Early postnatal hypoxia alters catecholaminergic system development and function in rats.
- Hypoxia-induced changes manifest as altered grooming, rearing, and stereotypy behaviors.
- While some drug responses normalized by adulthood, early hypoxia has lasting behavioral consequences.
Abstract:
We have previously reported alterations in a battery of behavioral functions in the rat following both intermittent and chronic prenatal hypoxia. In this species, the critical brain growth spurt for the catecholaminergic neurotransmitter system takes place in the late gestational and early postnatal period. In addition, postnatal stress can modify adult hypothalamic-pituitary-adrenal responsiveness. Following a given stress, administration of dopaminergic/adrenergic agonists/antagonists may elucidate subtle changes that are not apparent in routine behavioral and endocrine tests. To test the hypothesis that early postnatal hypoxia affects development of the catecholaminergic system and, thus, alters functional outcome, we performed the following study. We exposed 25 litters of Sprague-Dawley rats, each consisting of 10 male pups, to hypoxia (10.5% inspired O2) for 6 h/day (0900 to 1500 h) from postnatal day (P) 2 to 10. We also had 25 control (C) litters. We then performed a series of behavioral tests in immature and mature animals. Body weights were significantly decreased in hypoxic (H) animals from P10 to P100. At P21 we tested locomotor activity in an open-field paradigm with drug challenge (apomorphine, a dopamine receptor agonist, 0.025 and 0.1 mg/kg; or haloperidol, a dopamine receptor antagonist, 0.2 and 0.4 mg/kg). Grooming activity was significantly decreased in H animals at both apomorphine concentrations, compared to controls. Moreover, rearing activity was significantly increased in H animals under basal conditions and when challenged with 0.1 mg/kg apomorphine. Apomorphine (1.0 mg/kg)-induced stereotypy at P39 was significantly increased in H animals compared to controls. Open-field activity at 80 days revealed no significant differences in drug responsiveness between H and C animals.(ABSTRACT TRUNCATED AT 250 WORDS)