INCREASED LOSS OF BRAIN DNA IN THE NEONATAL VASOPRESSIN-DEFICIENT BRATTLEBORO RAT, BUT NOT IN NORMAL RAT TREATED WITH VASOPRESSIN ANTAGONIST

In order to establish whether vasopressin (VP) influences brain cell survival, [H-3]thymidine was injected in 10-day-old vasopressin-deficient Brattleboro rat pups, as well as in Wistar pups treated, neonatally, with the VP antagonist dP[Tyr(Me)2]VP followed by subsequent measurement of [H-3]DNA in olfactory bulbs and cerebellum days and weeks thereafter. Results show, first of all, that the incorporation of [H-3]thymidine into DNA was enhanced in the homozygous (HOM) Brattleboro, when compared with the heterozygous (HET; non-vasopressin-deficient) controls. The difference is due to the greater and prolonged tissue availability of [H-3]thymidine, possibly pointing to an altered thymidine uptake and/or metabolism. Between postnatal days 25 and 39 no differences were seen in [H-3]DNA content of the brain parts of the HET and Wistar control rats. For the HOM rats, however, a loss of [H-3]DNA was seen (up to 8%), indicating that increased postnatal brain cell death might occur in the mutant. The antagonist treatment in Wistar rat up to 21 days of age failed to show a similar effect. It is proposed that general growth impairments, rather than VP receptor-mediated effects, lead to the brain cell loss.