EVIDENCE THAT ACTIVATION OF THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS BYELECTRICAL-STIMULATION OF THE NORADRENERGIC A1 GROUP IS NOT MEDIATED BY NORADRENALINE

The paraventricular nucleus (PVN) of the hypothalamus, where the CRF-c ontaining neurosecretory cells controlling the hypothalamo-pituitary-a drenal (HPA) axis are located, receives a dense noradrenergic innervat ion from the A1 group of the caudal ventrolateral medulla. In the pres ent study we studied the relationship between release of noradrenaline (NA) in the PVN and activation of the HPA axis in response to electri cal stimulation of the A1 region. In the urethane-anesthetized male ra t, extracellular NA in the PVN was monitored on line by electrochemica l recording while the activity of the HPA axis was estimated by measur ement of ACTH in blood samples. A I min, 10 Hz stimulation evoked a si gnificant increase of extracellular NA in the PVN as well as an ACTH s urge 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 fr equency, the ACTH response appeared to plateau between 10 and 14 Hz. S pecific lesions of the noradrenergic terminals in the PVN, by bilatera l local administration of 6-hydroxydopamine, markedly reduced the ACTH response to stimulation. Intracerebroventricular injection of desmeth ylimipramine, a NA uptake inhibitor, enhanced the increase in extracel lular NA evoked by submaximal stimulation about 2.5-fold but did not m odify the corresponding ACTH response. Combined intracerebroventricula r 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 Al noradrenergic group projecting to the PVN. However, the inability of pharmacological manipulations which enhance or block central noradr energic transmission to influence the ACTH response suggests that the noradrenergic endings in the PVN originating from the Al group use a t ransmitter other than NA to activate the HPA axis at the PVN level.