Role of the lateral parabrachial nucleus in the control of sodium appetite

Abstract

.-In states of sodium deficiency many animals seek and consume salty solutions to restore body fluid homeostasis. These behaviors reflect the presence of sodium appetite that is a manifestation of a pattern of central nervous system (CNS) activity with facilitatory and inhibitory components that are affected by several neurohumoral factors. The primary focus of this review is on one structure in this central system, the lateral parabrachial nucleus (LPBN). However, before turning to a more detailed discussion of the LPBN, a brief overview of body fluid balance-related body-to-brain signaling and the identification of the primary CNS structures and humoral factors involved in the control of sodium appetite is necessary. Angiotensin II, mineralocorticoids, and extracellular osmotic changes act on forebrain areas to facilitate sodium appetite and thirst. In the hindbrain, the LPBN functions as a key integrative node with an ascending output that exerts inhibitory influences on forebrain regions. A nonspecific or general deactivation of LPBN-associated inhibition by GABA or opioid agonists produces NaCl intake in euhydrated rats without any other treatment. Selective LPBN manipulation of other neurotransmitter systems [e.g., serotonin, cholecystokinin (CCK), corticotrophin-releasing factor (CRF), glutamate, ATP, or norepinephrine] greatly enhances NaCl intake when accompanied by additional treatments that induce either thirst or sodium appetite. The LPBN interacts with key forebrain areas that include the subfornical organ and central amygdala to determine sodium intake. To summarize, a model of LPBN inhibitory actions on forebrain facilitatory components for the control of sodium appetite is presented in this review. sodium intake; angiotensin; electrolyte balance; thirst ANIMALS CONSTANTLY LOSE WATER and electrolytes to the external environment, but specific autonomic, hormonal, and behavioral mechanisms operate continuously to adjust and restore body fluid-electrolyte balance. The rate of loss from the kidneys is primarily controlled by neural and hormonal actions, but loss may also occur passively through the largely uncontrolled processes of respiration (evaporation), perspiration, transpiration, and salivation. These later modes of loss are referred to as insensible loss because they cannot be easily measured. Severe loss of both sodium and water may also occur in disorders associated with emesis and diarrhea. However, despite such ongoing challenges, the osmolarity and volume of body fluids are maintained within reasonably narrow limits, thus allowing normal metabolic and cardiovascular functions. Although renal mechanisms can slow water and sodium loss, the restoration of fluid homeostasis is only made possible by the mobilization of behaviors that result in the ingestion of water and sodium (usually NaCl). The behavioral responses of seeking out and consuming water and salty substances involve the motivational states of thirst and salt appetite. Salt appetite is also frequently referred to as sodium appetit...

Gabaergic and opioid receptors mediate the facilitation of NaCl intake induced by α2-adrenergic activation in the lateral parabrachial nucleus

“…The results also confirm at least in part the hypothesis that GABA and opioid receptors interact with multiple neurotransmitters independently from the hydration status of the animal [34]. Bicuculline and naloxone abolish 0.3 M NaCl and water intake induced respectively by muscimol and ␤-endorphin injected into the LPBN of satiated, fluid replete, rats [20,27,29].…”

“…In conclusion, the present and previous studies [19,34,35,38] suggest that moxonidine acting in ␣ 2 -adrenoceptors in the LPBN increases the release of GABA and opioids and blocks serotonin action, reducing the activity of the inhibitory mechanisms, which might enhance ingestive reactions and reduces rejection responses caused by the ingestion of 0.3 M NaCl and water, increasing the intake.…”

“…Moxonidine, however, has no effect on sodium or water intake when injected into the LPBN of satiated rats [21]. It has been hypothesized that the threshold to increase hypertonic sodium intake when GABA and opioid neurotransmission are activated is much lower than that required to increase NaCl intake when, for example, ␣ 2 -adrenoceptors are activated [34]. Dehydration or thirst-related signals decrease such threshold in the LPBN allowing the activation of ␣ 2 -adrenoceptors to recruit GABA and opioid mechanisms and so increase hypertonic NaCl intake.…”

“…However, it is still not possible to exclude interactions of ␣ 2-adrenoceptor mechanisms with other neurotransmitters/mechanisms (e.g. CCK, CRF, or glutamate) also known to reduce the inhibition of sodium intake [18,26,34,36]. Future studies may address this possibility.…”

Endogenous central amygdala mu-opioid receptor signaling promotes sodium appetite in mice

“…This mechanism is in agreement with our finding that the CeA was activated (displayed an increased number of Fos-positive neurons) following sodium gratification but not during sodium depletion when the sodiumrelated cues were absent. However, as the mice used in these Fos studies consumed large volumes of 0.3 M NaCl solution during the 10 min in which access was provided, it is also possible that the observed increase in CeA Fos may be due to indirect stimulation from the mouth and gastrointestinal tract (via the NTS and LPB) to signal the cessation of sodium consumption (30). A similar pattern of Fos immunoreactivity has been reported in rats, where sodium gratification also appeared to approximately double the number of CeA Fos-positive neurons compared with sodium-deficient rats that were killed 24 h after their last furosemide injection (a time point comparable to the present studies in mice) (31).…”