Arginine vasopressin (AVP) produced in the hypothalamic suprachiasmatic nuclei (SCN) plays a role in establishing neuroendocrine rhythms and, in particular, in regulating the corticotrope axis rhythm. It has recently been shown that AVP from SCN inhibits corticosteroid release. In order to investigate the influence of suprachiasmatic AVP on the different peptidergic systems through the hypothalamus, SCN neurons containing 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 hypothalamic and extrahypothalamic sites. Adrenocorticotrophic hormone (ACTH) concentration 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 immunoreactive content (24%, P < 0.01) and the decrease of AVP hybridized mRNA (33%, P < 0.01). This points to the efficiency of the microinjection in decreasing the production of AVP in the injection area. Modifications of the AVP contents in the two subdivisions of the hypothalamic paraventricular nucleus (PVN) were also observed. AVP contents decreased in the parvocellular subdivision (pPVN); this is coherent with the AVP depletion in SCN since pPVN is the major site of the SCN hypothalamic efferences. AVP content and AVP mRNA increased in the magnocellular subdivision (mPVN); this also confirms the difference in AVP synthesis regulation according to the PVN subdivisions. The microinjection did not modify AVP expression in supraoptic nuclei or oxytocin (OT) immunoreactive content in the main hypothalamic OT containing sites. Plasma 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 hypothalamo-pituitary-adrenal system since corticotrophin-releasing hormone (CRH) mRNA increased simultaneously by 24% (P < 0.05) in the PVN and the immunoreactive CRH content of the median eminence significantly decreased (26%, P < 0.05). Overall, our data confirm that AVP produced in the SCN inhibits the CRH-adrenocorticotrope axis in normal conditions, probably because of SCN projections of AVP neurons on the PVN.

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Central administration of angiotensin (Ang) II stimulates thirst and sodium intake via the AT-1 receptor. Mineralocorticoid pretreatment enhances Ang II-induced drinking of hypertonic salt solutions (i.e. the synergy theory) in Wistar and Sprague-Dawley rats. Electrophysiological experiments using iontophoretic application of Ang II, and the AT-1 receptor specific nonpeptide antagonist losartan, have shown excitation of neurones in the preoptic/medial septum region of urethane anaesthetised male Wistar rats. Deoxycorticosterone acetate (DOCA) pretreatment further enhanced this neuronal excitation to Ang II and reduced the responses to losartan. This generated the hypothesis that DOCA-enhanced Ang II-induced neuronal excitation was necessary for the enhanced salt intake of synergy theory. We tested this hypothesis in Fischer 344 rats that are known to have a low basal salt appetite and reduced sensitivity for i.c.v. Ang II. We compared the effect of DOCA pretreatment on i.c.v. Ang II-induced water and 2% NaCl intake in behaving adult male, Fischer rats, as well as preoptic/medial septum region neuronal responses to Ang II and losartan, using a seven-barrelled micro-iontophoretic electrode sealed to a recording electrode in urethane anaesthetised, male Fischer rats. Two groups were used: one pretreated with DOCA (0.5 mg/day for 3 days) and the other comprising controls, treated with isotonic saline. Ang II applied iontophoretically increased activity in 31% of the spontaneously active neurones. Following DOCA pretreatment, the responsiveness to Ang II (when applied after aldosterone) was increased. By contrast, in the behaving animals, water and 2% NaCl intake in response to i.c.v. Ang II were not enhanced by DOCA pretreatment. These results do not support the working hypothesis but could be interpreted as evidence for the existence of two separately modulated central Ang II systems: one responding to mineralocorticoids with increased neuronal activity and the other responsible for the Ang II-induced sodium appetite in conscious rats.