P.2.003 ATP as a regulator of anxiety-like behaviour in the paraventricular nucleus of rats

Abstract

the pup retrieval test, maternal aggression in the maternal defense test, and anxiety-related behavior on the elevated plus-maze. In a different set of dams, we assessed HPA axis activation upon specific CRF-R manipulation under basal and stressful conditions via repeated blood sampling and measured adrenocorticotropic hormone (ACTH) and corticosterone levels. Maternal care was differentially changed by CRF-R subtype-specific manipulation. Arched back nursing (ABN; one-way ANOVA; F4,32 = 4.81, p< 0.01), indicative of nursing quality, was improved by the CRF-R1 antagonist but also the CRF-R2 agonist (p = 0.03, each). The occurrence of total nursing (F4,32 = 12.87, p< 0.01), indicative of nursing quantity, was reduced by both agonists (p< 0.01, each). These results demonstrate that the receptor subtypes antagonize maternal care in the adBNST in contrast to their cooperation in the pBNST. Following stressful conditions, i.e. after maternal defense, ABN tended to be improved only by the CRF-R1 antagonist (t-test vs. control; t13 = −1.99, p = 0.06). Maternal aggression, maternal motivation, and anxiety were not affected by any manipulation. Regarding the HPA axis, we found that under basal conditions ACTH release (repeated measures ANOVA; F7.7,156 = 9.2, p< 0.01) was increased by the CRF-R1 agonist only (p< 0.01) while corticosterone release (F15.2,186 = 2.7, p< 0.01) was increased by both agonists (p< 0.05, each). Under stressful conditions, corticosterone levels remained high in CRF-R1 agonist-treated dams while a switch was observed in CRF-R2 agonist-treated dams (p< 0.05, each). Both antagonists prevented the stress-induced increase in corticosterone (p< 0.05, each). These results indicate that intra-adBNST activation of both receptor subtypes activates the HPA axis under basal conditions whereas in stressful situations CRF-R1 and CRF-R2 act in an antagonizing manner. In conclusion, maternal behavior is differentially regulated by CRF-R1 and CRF-R2 depending on the site of activation within the BNST. Moreover, altered HPA axis activity might be involved in or even responsible for the observed changes in behavioral patterns. These data extend our basic understanding of the maternal brain and provide new insights into potential dysregulations postpartum.