Cognitive, Behavioral, and Systems NeuroscienceResearch PaperNa+ appetite induced by depleting extracellular fluid volume activates the enkephalin/mu-opioid receptor system in the rat forebrain

In Na+ appetite neurobiology, it is essential to investigate whether endogenous opioids modulate the output of the neural substrates that are involved in both the detection and integration of Na+ deficiency and the motivational aspect of Na+ intake. Thus, evaluating the recruitment dynamics of enkephalin (ENK)-containing and/or mu-opioid receptor (μ-OR)-expressing neurons in close correlation with the hydromineral state of the rat might provide useful information regarding the role of the opioid system in regulating the central network that controls water and Na+ intake. Furosemide was used to deplete both fluid volume and the Na+ content of the extracellular fluid (ECF) compartment when combined with water repletion and a short-term Na+-free diet. Na+ restoration in the ECF compartment was achieved by providing unrestricted access to both saline (0.3 M NaCl) and water. Combining in situ hybridization (against ENK and μ-OR mRNA) and immunohistochemistry (against Fos) revealed a specific pattern of hypovolemia-induced Fos expression in the enkephalinergic subpopulations of the central amygdala, in the oval nucleus of the bed nucleus of the stria terminalis and in the nucleus accumbens shell. Hypovolemia also induced transient Fos expression in μ-OR-expressing neurons in the same nuclei and in the median preoptic nucleus and subfornical organ. However, this specific hydromineral state did not activate the ENK and/or μ-OR-expressing neurons in the lateral parabrachial nucleus or in the medial nucleus of the solitary tract. These results implicate the ENK/μ-OR system as a putative facilitator of Na+ intake in discrete regions of the forebrain, possibly by modulating the hedonic and reward value of Na+ by increasing ENK release in these regions.

▶Combined episodes of Na+ depletion and Na+ repletion activate the salt-intake network. ▶Contribution of the enkephalin/mu-opioid receptor system to the salt-intake network is examined. ▶ENK and μ-OR neurons are activated in discrete regions of the forebrain. ▶ ENK/μ-OR system likely modulates the forebrain output of the salt-intake network. ▶ENK/μ-OR system might modulate the hedonic and reward value of Na+ and water.