Depressive- and anxiety-like behaviors and stress-related neuronal activation in vasopressin-deficient female Brattleboro rats

• AVP aggravates anxiety- and depression-like behavior in females.
• The regulatory role of AVP might be more important in depression than in anxiety.
• The impact of AVP-deficiency was sex dependent on social and memory function.
• In females behavioral regulation correlated significantly with stress-hormones.
• In females AVP-deficiency led to blunted stress-activation of some brain areas.

Vasopressin can contribute to the development of stress-related psychiatric disorders, anxiety and depression. Although these disturbances are more common in females, most of the preclinical studies have been done in males.We compared female vasopressin-deficient and +/+ Brattleboro rats. To test anxiety we used open-field, elevated plus maze (EPM), marble burying, novelty-induced hypophagia, and social avoidance tests. Object and social recognition were used to assess short term memory. To test depression-like behavior consumption of sweet solutions (sucrose and saccharin) and forced swim test (FST) were studied. The stress–hormone levels were followed by radioimmunoassay and underlying brain areas were studied by c-Fos immunohistochemistry.In the EPM the vasopressin-deficient females showed more entries towards the open arms and less stretch attend posture, drank more sweet fluids and struggled more (in FST) than the +/+ rats. The EPM-induced stress-hormone elevations were smaller in vasopressin-deficient females without basal as well as open-field and FST-induced genotype-differences. On most studied brain areas the resting c-Fos levels were higher in vasopressin-deficient rats, but the FST-induced elevations were smaller than in the +/+ ones.Similarly to males, female vasopressin-deficient animals presented diminished depression- and partly anxiety-like behavior with significant contribution of stress-hormones. In contrast to males, vasopressin deficiency in females had no effect on object and social memory, and stressor-induced c-Fos elevations were diminished only in females. Thus, vasopressin has similar effect on anxiety- and depression-like behavior in males and females, while only in females behavioral alterations are associated with reduced neuronal reactivity in several brain areas.