β-Arrestin-2 Regulates Sodium Taste Processing.

BACKGROUND

Altered detection and preference for sodium are associated with increased sodium intake, and increased sodium intake is associated with increased risk of hypertension. AT1R (angiotensin II type 1 receptor) second-messenger signaling is mediated and modulated by ARRB2 (β-arrestin-2), and both AT1R and ARRB2 in the brain influence sodium intake. Here, we examined the hypotheses that ARRB2 influences sodium taste hedonics and that these effects involve AT1R.

METHODS

Sodium intake behaviors and hedonic reactions of mice carrying a null mutation of the endogenous ARRB2 gene (Arrb2-KO [knockout] mice) were evaluated using 2-bottle choice testing, brief-access paradigms, and intraoral taste reactivity assays.

RESULTS

Arrb2-KO mice of both sexes exhibited dose-dependent increases in licking to sodium chloride and sucrose, but not quinine or citric acid, during a brief-access paradigm; rapid recovery of spontaneous isotonic saline intake after acute adulteration by quinine or exposure to hypertonic saline; persistently elevated isotonic saline intake even when dietary sodium content was increased from 0.15% to 1.00%; and reduced aversive reactions to acute intraoral isotonic saline. Finally, the spontaneous increase in isotonic saline intake by Arrb2-KO mice was abolished by administration of the AT1R antagonist losartan.

CONCLUSIONS

Together, these findings highlight a major role for ARRB2 in sodium taste processing, which appears to be mediated through an AT1R-dependent mechanism.