ALTERED CATECHOLAMINERGIC BEHAVIORAL AND HORMONAL RESPONSES IN RATS FOLLOWING EARLY POSTNATAL HYPOXIA

We have previously reported alterations in a battery of behavioral fun ctions in the rat following both intermittent and chronic prenatal hyp oxia. In this species, the critical brain growth spurt for the catecho laminergic 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/antagonis ts may elucidate subtle changes that are not apparent in routine behav ioral 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 expo sed 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 pos tnatal day (P) 2 to 10. We also had 25 control (C) litters. We then pe rformed a series of behavioral tests in immature and mature animals. B ody weights were significantly decreased in hypoxic (H) animals from P 10 to P100. At P21 we tested locomotor activity in an open-field parad igm with drug challenge (apomorphine, a dopamine receptor agonist, 0.0 25 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 ani mals at both apomorphine concentrations, compared to controls. Moreove r, rearing activity was significantly increased in H animals under bas al conditions and when challenged with 0.1 mg/kg apomorphine. Apomorph ine (1.0 mg/kg)-induced stereotypy at P39 was significantly increased in H animals compared to controls. Open-field activity at 80 days reve aled no significant differences in drug responsiveness between H and C animals. The corticosterone response to clonidine at P150 showed sign ificantly earlier rise of corticosterone concentrations in the H anima ls. However, restraint stress showed no difference in corticosterone r esponsiveness between the two treatment groups. We conclude that relat ively mild, early, postnatal hypoxia can result in altered activity of the dopaminergic and adrenergic neurotransmitter systems, which affec t pharmacological responses.