Anxiogenic role of vasopressin during the early postnatal period: maternal separation-induced ultrasound vocalization in vasopressin-deficient Brattleboro rats

Amino Acids. 2015 Nov;47(11):2409-18. doi: 10.1007/s00726-015-2034-x. Epub 2015 Jul 2.


Both animal and human studies suggest that in adulthood, plasma vasopressin level correlates well with anxiety. Little is known about the mood regulation during the perinatal period. Here, we aim to investigate the influence of vasopressin on anxiety during the early postnatal age. As a sign of distress, rat pups emit ultrasonic vocalizations (USVs) when they are separated from their mother. This USV was detected in 7- to 8-day-old vasopressin-deficient Brattleboro pups, and they were compared to their heterozygote littermates and wild-type pups. The results were confirmed by V1b antagonist treatment (SSR149415 10 mg/kg ip 30 min before test) in wild-types. Chlordiazepoxide (3 mg/kg ip 30 min before test)-an anxiolytic-was used to test the interaction with the GABAergic system. At the end of the test, stress-hormone levels were measured by radioimmunoassay. Vasopressin-deficient pups vocalized substantially less than non-deficient counterparts. Treatment with V1b antagonist resulted in similar effect. Chlordiazepoxide reduced the frequency and duration of the vocalization only in wild-types. Reduced vocalization was accompanied by smaller adrenocorticotropin levels but the level of corticosterone was variable. Our results indicate that the anxiolytic effect of vasopressin deficiency (both genetic and pharmacological) exists already during the early postnatal age. Vasopressin interacts with the GABAergic system. As mood regulation does not go parallel with glucocorticoid levels, we suggest that vasopressin might have a direct effect on special brain areas.

Keywords: Anxiety; Chlordiazepoxide; GABA; Postnatal period; SSR149415; Ultrasound vocalization; Vasopressin.

MeSH terms

  • Adrenocorticotropic Hormone / metabolism
  • Affect / drug effects*
  • Animals
  • Anxiety / metabolism*
  • Chlordiazepoxide / pharmacology
  • Corticosterone / metabolism
  • Female
  • Humans
  • Postpartum Period / metabolism*
  • Rats
  • Rats, Brattleboro
  • Vasopressins* / metabolism
  • Vasopressins* / pharmacology
  • Vocalization, Animal / drug effects*


  • Vasopressins
  • Chlordiazepoxide
  • Adrenocorticotropic Hormone
  • Corticosterone