Homozygous Brattleboro rats display attenuated conditioned freezing responses.

In the present study we examined the influence of arginine vasopressin (AVP) on conditioned freezing behavior to aversive shock treatment by comparing the responses of Brattleboro homozygous (DI) rats, Brattleboro heterozygous (HZ) rats, and Long-Evans (LE) rats. Each animal was placed in a sound-attenuated shock chamber on the training day and given a series of 3 footshocks. On the following 4 consecutive days the rats were placed in the chambers where they had received their shock and levels of spontaneous freezing were evaluated. Levels of circulating vasopressin-associated neurophysin (NP) were subsequently determined in each rat strain. For each of the 4 test days, DI rats displayed significantly less freezing behavior when compared with LE rats and HZ rats. HZ rats displayed trends towards attenuated freezing responses when compared with LE rats. The data indicate that a relationship exists between the levels of central nervous system (CNS) and circulating AVP, and the amount of freezing displayed by each strain. These preliminary results suggest that vasopressin may be involved in appropriate autonomic and emotional responses to fearful stimuli in fear conditioning paradigms.

Elevated serum oxytocin of the vasopressin-deficient Brattleboro rat is present throughout life and is not sensitive to treatment with vasopressin.

The postnatal developmental course of the enhanced OT serum level of the vasopressin-deficient (homozygous) Brattleboro rat was investigated radioimmunochemically together with the response to treatment with Pitressin tannate. Compared with heterozygous Brattleboro (control) pups, in which serum OT appeared to have an adult value from birth onwards (about 10 pmol/l), homozygous rats had approximately 2-fold enhanced OT serum level throughout early development. Between day 55 and adulthood the levels of OT rose further to 40-50 pmol/l. A 3-day treatment with Pitressin tannate both in the period before or after the age (day 16) at which the polyuria of the homozygous Brattleboro mutant can be revealed, failed to reduce the serum OT. It was therefore concluded that the high OT serum levels in the vasopressin-deficient Brattleboro rat are not induced by osmotic imbalance, but probably originates from functional teratological aspects of the mutation.

The Brattleboro rat: normal growth hormone secretion, decreased hepatic growth hormone receptors and low plasma somatomedin activity.

Three-month-old male Brattleboro rats with hereditary diabetes insipidus (DI) present a growth defect; Brattleboro rats were studied together with age-matched Long-Evans (LE) rats. Pituitary growth hormone (GH) content was comparable in both groups of rats. Pulsatile GH release and mean 6 h GH plasma levels did not appear significantly different in chronically catheterized DI and control animals. In parallel with the growth defect, the plasma somatomedin bioactivity was significantly lower in DI than in LE rats. The specific binding of [125I]iodo-hGH to liver microsomal membranes of DI rats was 59.7% that of controls. The number of the GH binding sites rather than the affinity of the binding was decreased. The specific binding of [125I]iodo-insulin was oppositely affected by the DI state: it was 1.5 times higher in liver membranes of DI rats than in membranes of LE rats. These findings make a non-specific effect of the DI state on liver membrane proteins unlikely. The Brattleboro rats present a growth failure without reduction of their GH secretion. The decreased number of the hepatic GH receptors and the subsequent low plasma somatomedin activity could explain the growth retardation of the DI rats.