Sensitization of sodium appetite: evidence for sustained molecular changes in the lamina terminalis

Abstract

Animals with a history of sodium depletions exhibit increases in salt intake, a phenomenon described as the sensitization of sodium appetite. Using a novel experimental design, the present experiments investigated whether putative molecular markers of neural plasticity and changes in the message for components of the brain renin-angiotensin-aldosterone-system (RAAS) accompany the sensitization of sodium appetite. An initial set of experiments examined whether the glutamatergic N-methyl-d-aspartate receptor antagonist MK-801 would attenuate sodium appetite sensitization and prevent changes in mRNA expression associated with sensitization. Rats with repeated sodium depletions exhibited enhanced sodium appetite and mRNA expression for components of the RAAS in areas along the lamina terminalis (LT), a region of the brain that is important for the regulation of body fluid homeostasis, and these effects were significantly attenuated by MK-801 pretreatment. A second set of experiments investigated whether successive sodium depletions would elevate sodium intake and induce a pattern of fos-B staining consistent with the Δfos-B isoform in areas along the LT. The pattern of fos-B staining in the subfornical organ was consistent with the characteristics of Δfos-B expression. Specifically, fos-B/Δfos-B expression was increased 4 days after the last of a series of sodium depletions, fos-B/Δfos-B expression was nearly absent in control rats, and the quantity of fos-B/Δfos-B staining was directly associated with a history of sodium depletions. These findings demonstrate that the sensitization of sodium appetite is associated with sustained molecular alterations in the LT that are indicative of neural plasticity and upregulation of the central RAAS.

Water deprivation-partial rehydration induces sensitization of sodium appetite and alteration of hypothalamic transcripts

“…The elevated levels we found for Agt gene is also consistent with the increased sodium intake of animals with hyperactive brain RAS, inherited, such as in SHR, or genetically engineered, such as in transgenic mice overexpressing neuronal Agt or angiotensin AT 1 receptor genes (18,27). The effect on Agt is also in line with ANG II sensitizing the brain to become more responsive to the pressor effect of ANG II itself and sodium depletion (17,42). In addition, the increased hypothalamic mRNA expression of Anpep induced by WD-PR in HTZ suggests that angiotensins other than ANG II are associated with history of WD-PR.…”

“…Several factors like age, sex, and taste influence sodium intake (8,15,19,41). In addition, ANG II is an established key mediator of sodium appetite sensitization associated with sodium loss (3,17,31,36). Circumstantial evidence also suggests that sensitization to sodium appetite induced by recurrent episodes of WD-PR involves activation of brain ANG II receptors.…”

The biopsychology of salt hunger and sodium deficiency

“…If this is true, then many of the neural processes that are responsible for sodium appetite (e.g., changes in neurotransmitter release, mRNA expression, or receptor expression) should still be exhibited long after body sodium has been restored. Recent evidence supports this idea as repeated episodes of sodium deficiency produce a long-lasting elevation in mRNA expression across the LT for the angiotensin II receptor type 1, mineralocorticoid receptor, and serum- and glucocorticoid-induced kinase, an intracellular messenger that is activated downstream from the mineralocorticoid receptor [60, 74, 102]. Additionally, sodium depletion appears to produce a long-lasting increase in the expression of Δ fos -B, a molecular marker that has been associated with neuroplasticity, in the SFO [60, 103, 104].…”

Estradiol and osmolality: Behavioral responses and central pathways

“…In previous studies, sex differences in NaCl intake have been reported after Furosemide ([7] but see [43]). We opted to employ a single episode of Furosemide-induced sodium depletion in order to assess the possibility of estradiol effects on osmotic regulation prior to the establishment of behavioral changes that appear to involve long-term modulation of central pathways [29, 40]. …”