Hypothalamic vasopressin system regulation by maternal separation: Its impact on anxiety in rats

Maternal separation (MS) has been used to model the causal relationship between early life stress and the later stress-over-reactivity and affective disorders. Arginine vasopressin (AVP) is among several factors reported to be abnormal. The role of AVP on anxiety is still unclear. In order to further investigate this causal relationship and its possible role in anxiogenesis, male rat pups were separated from their dams for 3 h daily (3hMS) from post-natal day (PND) 2 to PND15. Fos expression in AVP+ neurons in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) triggered by 3hMS, and AVP-mRNA expression, were examined at PND10 and PND21 respectively, whereas AVP-mRNA expression, PVN and SON volumes and plasma AVP concentration were assessed in adulthood. Elevated plus maze test (EPM) and Vogel conflict test (VCT) were also performed to evaluate unconditioned and conditioned anxious states at PND70-75. At PND10, a single 3hMS event increased Fos expression in AVP+ neurons fourfold in PVN and six to twelvefold in SON. AVP-mRNA was over-expressed in whole hypothalamus, PVN and SON between 122% and 147% at PND21 and PND63. Volumes of AVP-PVN and AVP-SON measured at PND75 had marked increases as well as AVP plasma concentration at 12 h of water deprivation (WD). MS rats demonstrated a high conditioned anxious state under VCT paradigm whereas no difference was found under EPM. These data demonstrate direct relationships between enhanced AVP neuronal activation and a potentiated vasopressin system, and this latter one with high conditioned anxiety in MS male rats.

► Maternal separation (MS) activates Fos/AVP in PVN and SON neurons at PND10. ► AVP mRNA expressions in hypothalamus were enhanced at PND21 and PND63. ► AVP-PVN and AVP-SON nuclei measured at PND75 were markedly enlarged. ► Significant increase of anxiety was observed through Vogel conflict test. ► Data indicated direct relationship between aberrant AVP system and anxiety.