title: Evidence that activation of the hypothalamo-pituitary-adrenal axis by electrical stimulation of the noradrenergic A1 group is not mediated by noradrenaline.
abstract: The paraventricular nucleus (PVN) of the hypothalamus, where the CRF-containing neurosecretory cells controlling the hypothalamo-pituitary-adrenal (HPA) axis are located, receives a dense noradrenergic innervation from the A1 group of the caudal ventrolateral medulla. In the present study we studied the relationship between release of noradrenaline (NA) in the PVN and activation of the HPA axis in response to electrical stimulation of the A1 region. In the urethane-anesthetized male rat, extracellular NA in the PVN was monitored on line by electrochemical recording while the activity of the HPA axis was estimated by measurement of ACTH in blood samples. A 1 min, 10 Hz stimulation evoked a significant increase of extracellular NA in the PVN as well as an ACTH surge in blood. The NA and ACTH response evoked by stimulation in the 3- to 14-Hz range were found to be frequency dependent. However, whilst the NA response increased in an exponential manner with respect to frequency, the ACTH response appeared to plateau between 10 and 14 Hz. Specific lesions of the noradrenergic terminals in the PVN, by bilateral local administration of 6-hydroxydopamine, markedly reduced the ACTH response to stimulation. Intracerebroventricular injection of desmethylimipramine, a NA uptake inhibitor, enhanced the increase in extracellular NA evoked by submaximal stimulation about 2.5-fold but did not modify the corresponding ACTH response. Combined intracerebroventricular injection of alpha- and beta-adrenergic antagonists, phentolamine and propanolol respectively, did not prevent the ACTH response evoked by stimulation. Following stimulation of the caudal ventrolateral medulla, the ACTH response thus appears to result from the stimulation of the A1 noradrenergic group projecting to the PVN. However, the inability of pharmacological manipulations which enhance or block central noradrenergic transmission to influence the ACTH response suggests that the noradrenergic endings in the PVN originating from the A1 group use a transmitter other than NA to activate the HPA axis at the PVN level.
authors.affiliation: Inserm U 171 and CNRS URA 1195, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.
authors.forename: S E
authors.initials: SE
authors.lastname: Gartside
authors.forename: M F
authors.initials: MF
authors.lastname: Suaud-Chagny
authors.forename: M
authors.initials: M
authors.lastname: Tappaz
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D004558:Electric Stimulation; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000324:Adrenocorticotropic Hormone; D011433:Propranolol; D009638:Norepinephrine; D010646:Phentolamine