ARGININE-VASOPRESSIN (AVP) DEPLETION IN NEURONS OF THE SUPRACHIASMATIC NUCLEI AFFECTS THE AVP CONTENT OF THE PARAVENTRICULAR NEURONS AND STIMULATES ADRENOCORTICOTROPIC HORMONE-RELEASE

Arginine vasopressin (AVP) produced in the hypothalamic suprachiasmati c nuclei (SCN) plays a role in establishing neuroendocrine rhythms and , in particular, in regulating the corticotrope axis rhythm. It has re cently been shown that AVP from SCN inhibits corticosteroid release. I n order to investigate the influence of suprachiasmatic AVP on the dif ferent peptidergic systems through the hypothalamus, SCN neurons conta ining AVP were functionally lesioned by using toxins associated with a cytotoxic monoclonal antibody (MAb) raised against AVP Six days later , the AVP contents and AVP mRNA were measured in different hypothalami c and extrahypothalamic sites. Adrenocorticotrophic hormone (ACTH) con centration was also measured in plasma. Microinjection of the AVP-MAb/ toxin mixture into SCN brought about a significant decrease in the AVP expression in SCN. This is demonstrated by the decrease in the AVP im munoreactive content (24%, P < 0.01) and the decrease of AVP hybridize d mRNA (33 %, P < 0.01). This points to the efficiency of the microinj ection in decreasing the production of AVP in the injection area. Modi fications of the AVP contents in the two subdivisions of the hypothala mic paraventricular nucleus (PVN) were also observed. AVP contents dec reased in the parvocellular subdivision (pPVN); this is coherent with the AVP depletion in SCN since pPVN is the major site of the SCN hypot halamic efferences. AVP content and AVP mRNA increased in the magnocel lular subdivision (mPVN); this also confirms the difference in AVP syn thesis regulation according to the PVN subdivisions. The microinjectio n did not modify AVP expression in supraoptic nuclei or oxytocin (OT) immunoreactive content in the main hypothalamic OT containing sites. P lasma ACTH values were double (P < 0.02) the values measured under non -specific IgG treatment 10 hr after lights on. This probably resulted from the stimulation of the hypothalamopituitary-adrenal system since corticotrophin-releasing hormone (CRH) mRNA increased simultaneously b y 24% (P < 0.05) in the PVN and the immunoreactive CRH content of the median eminence significantly decreased (26%,P < 0.05). Overall, our d ata confirm that AVP produced in the SCN inhibits the CRH-adrenocortic otrope axis in normal conditions, probably because of SCN projections of AVP neurons on the PVN. (C) 1997 Wiley-Liss, Inc.