Hippocampal adenosine A1 and A2A receptor imbalance is associated with anxiety-like behavior in carioca high- and low-freezing rats

Abstract

Data from clinical studies implicate adenosine in different types of anxiety disorders. Pharmacological and genetic manipulation of A1 and A2A adenosine receptors (A1R and A2AR) suggest that each contributes separately to regulating anxious states. This study aimed to perform a comparative neurochemical analysis of these receptors in animal models with a genetic basis of anxiety. Male Wistar rats previously selected through the freezing paradigm and characterized as high (CHF) and low (CLF) anxiety-like responses were compared to the control group (CTL). Animals were submitted to behavioral tests to evaluate anxiety-like behavior and declarative memory, and to biochemical and immunohistochemical analyses to evaluate the level and localization of A1R and A2AR in the hippocampus. In the elevated plus-maze, the CHF group was more anxious than the control and CLF groups. No statistical differences were found in the object recognition task among groups. Biochemical analyses showed a significant increase in A1R content for CHF in the dorsal hippocampus compared to the control group. On the other hand, the ventral hippocampus presented a decrease in A1R level for CHF and an increase for CLF compared to the control group. Concerning A2AR, data showed that the CLF group presented an increase in the dorsal hippocampus and a decrease in the ventral hippocampus compared to the control group. Together, these results support the hypothesis that the differential level of adenosine receptors in the hippocampus may modulate different aspects of anxiety-like behavior.