EARLY POSTNATAL APPEARANCE OF ENHANCED NORADRENALINE CONTENT IN THE BRAIN OF VASOPRESSIN-DEFICIENT BRATTLEBORO RAT - NORMAL ADRENOCEPTOR DENSITIES AND ABERRANT INFLUENCES OF VASOPRESSIN TREATMENT

The course of postnatal development of noradrenaline (NA) and its unco njugated free metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), as we ll as the influence on early chronic vasopressin treatment, were inves tigated in various brain regions of the hereditary vasopressin-deficie nt (homozygous di/di) Brattleboro rat. In addition, the densities of t he adrenergic receptor subtypes were measured in adult brain. Brain NA levels of di/di pups appeared enhanced already at 7 days of age when compared with data of heterozygous (+/di) controls. This was also seen in areas not known to receive a vasopressinergic input, e.g. the fron tal cortex, Levels of MHPG also differed between genotypes, but change s were slight and either a decrease or increase, depending on age and region tested. Saturation analyses of alpha(1)-, alpha(2)-, and beta-a drenoceptor binding on crude membrane preparations of some brain regio ns revealed no differences in adulthood. Chronic treatment with vasopr essin between 6 and 13 days of age reduced the enhanced NA brain level s throughout the brain of the di/di Brattleboro pups. The known vasopr essin-mediated enhancement of NA turnover in adult brain was also meas urable in +/di pups of this neonatal period (MHPG/NA ratios), indicati ng the early maturation of the interaction of vasopressinergic and NAe rgic systems. However, the dose-response in the di/di Brattleboro rat was biphasic with a decrease at a low dose of vasopressin. Since chang es were found throughout the brain, it was concluded that vasopressin deficiency had altered the maturation of NA neurons of the locus coeru leus which may be due to the absence of a presumed inhibitory control of vasopressin on synthesis and storage mechanisms at the perikaryal l evel.