Altered catecholaminergic behavioral and hormonal responses in rats following early postnatal hypoxia

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 O 2) 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. The corticosterone response to clonidine at P150 showed significantly earlier rise of corticosterone concentrations in the H animals. However, restraint stress showed no difference in corticosterone responsiveness between the two treatment groups. We conclude that relatively mild, early, postnatal hypoxia can result in altered activity of the dopaminergic and adrenergic neurotransmitter systems, which affect pharmacological responses.