Reduced noradrenergic tone to the hypothalamic paraventricular nucleus contributes to the stress hyporesponsiveness of lactation.
Lactation in mammals is accompanied by a marked decrease in stress responsiveness that we previously attributed, in part, to a reduction in noradrenergic (NA) innervation of hypothalamic paraventricular nucleus (PVN) neurons controlling neuroendocrine stress responses. In the present study, we compared in-vivo PVN catecholamine secretion by microdialysis between nonlactating and lactating females and tested the effects of NA alpha-1 and alpha-2 receptor antagonists (corynanthine and idazoxan, respectively) on the acute stress response of lactating and virgin female rats. To determine if PVN alpha-adrenoreceptor density, affinity, or synthesis, changes as a function of lactation, we performed receptor autoradiography, Scatchard analysis and in situ hybridization of alpha-adrenoreceptors. Densitometric analysis of the alpha-adrenoreceptors in the supraoptic nucleus (SON) was used to evaluate changes in magnocellular neurons. Endogenous PVN norepinephrine release under basal conditions was lower in lactating females than in females who had their pups removed for 2 days, and microdialysate concentrations of adrenaline and MHPG were attenuated in lactating females. Alpha-2 adrenoreceptor density in the PVN showed a significant decrease from lactation day 3 to lactation days 10-12 and a reduction to 40% of virgin controls on days 10-20 of lactation. A similar pattern was observed for the SON. The affinity of hypothalamic alpha-2 adrenoreceptors was reduced as a function of lactation. Alpha-1 adrenoreceptor density in the PVN and in the hypothalamus rose as a function of lactation, although the affinity of these receptors was not altered. In contrast, alpha-1D adrenoreceptor subtype mRNA expression in the PVN decreased in middle lactating females (day 10) compared to virgins. Intracerebroventricular (i.c.v.) application of idazoxan, significantly increased the ACTH response to swim stress in virgin females, but had the opposite effect in lactating females. In contrast, i.c.v. corynanthine treatment significantly decreased the ACTH response in virgins, but not in lactating females. Overall, these data suggest that the secretion of NA in the PVN is reduced during lactation, and that the ability of PVN parvocellular neurons to respond to changes in synaptic NA levels (i.e. after stress) is also altered.
Douglas Hospital Research Center, Department of Psychiatry, Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada.
D J
DJ
Toufexis
K V
KV
Thrivikraman
P M
PM
Plotsky
D A
DA
Morilak
N
N
Huang
C D
CD
Walker
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D015536:Down-Regulation; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D007774:Lactation; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000145:classification; D013312:Stress, Physiological / Q000503:physiopathology*
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D008734:Methoxyhydroxyphenylglycol; D000324:Adrenocorticotropic Hormone; D009638:Norepinephrine; D004837:Epinephrine