Abstract P170: Beta-arrestin-2 Sustains Experience-dependent Plasticity Of Sodium Ingestive Behavior

Abstract

Elevated sodium (Na) intake is a risk factor for hypertension. Na “appetite” is defined by the persistence of Na consumption despite adverse conditions and is commonly assessed through ingestion of aversive NaCl solutions. β-arrestins interact with many G Protein-Coupled Receptors (GPCR), including the Angiotensin II Type 1 Receptor (AT 1 R). β-arrestins play roles in many physiological processes including regulation of cardiovascular function, sensory processing, and energy metabolism. Recent work published by our group concluded that β-arrestin-2 deficient (Arrb2 KO ) mice exhibited increased ingestion of NaCl solutions even in the absence of physiological need. Thus, we hypothesize that β-arrestin-2 plays a role in experience-based Na seeking behavior and elevated NaCl consumption. To explore this question, mice were first presented with a 2-bottle choice of water and 0.15 NaCl.; then exposed to aversive 0.3 M NaCl exclusively for 24h; followed by the same 2-bottle choice as at baseline. Usually, this manipulation would yield a reduction in preference for previously preferred concentrations of NaCl, demonstrating experience-based plasticity of NaCl preference. At baseline, male Arrb2 KO mice exhibited the expected increase in preference for 0.15 M NaCl vs water (control n=14, 34±5%; Arrb2 KO n=10, 55±7%, p<0.01). Following 24h hypertonic (0.3 M) saline exposure, both groups displayed a decrease in 0.15 M NaCl solution intake and preference (days 1+2 after exposure: 10±2% vs 21±4%, p<0.01 vs baseline within each group, and p=0.15 between groups). While control mice maintained this significant suppression of preference for 0.15 M NaCl beyond one week after 24h 0.3 M NaCl exposure (e.g., days 7+8 after exposure: controls 22±3% p=0.01 vs baseline), preference of Arrb2 KO mice for 0.15 M NaCl returned to baseline levels within days (e.g., days 7+8 Arrb2 KO 45±9%, p=0.08 vs baseline, and p<0.01 vs control). This supports the idea that Arrb2 is implicated in Na ingestive behaviors, potentially influencing memory maintenance and retrieval. Future studies aim to characterize the role of Arrb2 downstream of the AT 1 R within specific brain regions in Na consummatory behaviors.