The effect of norepinephrine (NOR) has been investigated in 8-day-old newborn rats of both sexes subjected to stress by 2 min ether inhalation or sham stress. The animals were sacrificed either before or 2 and 32 min after the stress or the sham stress prodecure was started. Investigations were also performed on newborns bearing neurotoxic lesions of the arcuate nucleus by neonatal treatment with monosodium-L-glutamate. The effect of NOR was also investigated in vitro on incubated pars distalis. ACTH concentrations in the pituitary, plasma, and the incubation medium were determined by radioimmunoassay. NOR at the dose of 0.2 µg/g was unable to affect plasma ACTH levels during a period of 60 min in unstressed newborns, in contrast to higher doses (0.5, 1, and 5.0 µg/g) which elicited a sharp rise in plasma ACTH levels. Then, NOR was injected (0.2 µg/g) to male and female pups 15 min before the stress or sham stress procedure. 32 min after the beginning of ether inhalation, the pituitary response was greater in NOR-injected than in saline-injected males; in NOR-treated females the rise in plasma ACTH levels was higher at 2 and 32 min than in saline-injected animals. At this latter time, plasma ACTH levels were similar in NOR-treated males and females, while in saline-treated newborns, the response to ether stress was greater and more longlasting in females than in males. No significant rise in plasma ACTH levels was observed in sham-stressed pups. The response to ether inhalation of saline- or NOR-treated males and females was significantly reduced by the α-blocking drug phenoxybenzamine (2 µg/g), but not by the β-blocking agent propranolol (5 µg/g) given to the animals 30 min before the beginning of the stress procedure. The ACTH contents of the pars distalis and pars neurointermedia were unchanged by sham stress or ether stress performed on saline- or NOR-treated animals. Neurotoxic lesions of the arcuate nucleus by neonatal treatment with monosodium glutamate did not significantly affect the basal level of plasma ACTH or its evolution in both sexes in response to ether inhalation. In vitro NOR did not affect the basal or the CRF-induced stimulation of ACTH release. The present data are consistent with an α-stimulatory effect of NOR on the neuroendocrine pathways involved in the pituitary response of the newborn rat to ether stress and suggested mediation through central nervous system rather than direct pituitary actions. The arcuate nucleus was not involved in that type of response.

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