Early postnatal appearance of enhanced noradrenaline content in the brain of vasopressin-deficient Brattleboro rat; normal adrenoceptor densities and aberrant influences of vasopressin treatment

Abstract

The course of postnatal development of noradrenaline (NA) and its unconjugated free metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), as well as the influence on early chronic vasopressin treatment, were investigated in various brain regions of the hereditary vasopressin-deficient (homozygous di/di) Brattleboro rat. In addition, the densities of the 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 frontal cortex. Levels of MHPG also differed between genotypes, but changes were slight and either a decrease or increase, depending on age and region tested. Saturation analyses of alpha 1-, alpha 2-, and beta-adrenoceptor binding on crude membrane preparations of some brain regions revealed no differences in adulthood. Chronic treatment with vasopressin between 6 and 13 days of age reduced the enhanced NA brain levels throughout the brain of the di/di Brattleboro pups. The known vasopressin-mediated enhancement of NA turnover in adult brain was also measurable in +/di pups of this neonatal period (MHPG/NA ratios), indicating the early maturation of the interaction of vasopressinergic and NAergic systems. However, the dose-response in the di/di Brattleboro rat was biphasic with a decrease at a low dose of vasopressin. Since changes were found throughout the brain, it was concluded that vasopressin deficiency had altered the maturation of NA neurons of the locus coeruleus which may be due to the absence of a presumed inhibitory control of vasopressin on synthesis and storage mechanisms at the perikaryal level.