In rat brain, the detection and integration of chemosensory and neural signals are achieved, inter alia, by the median preoptic nucleus (MnPO) during a disturbance of the hydromineral balance. This is allowed through the presence of the sodium (Na+) sensor neurons. Interestingly, enkephalins and mu-opioid receptors (μ-ORs) are known for their role in ingestive behaviors and have previously been shown to regulate the excitability of MnPO neurons following a single Na+ depletion. However, little is known about the role of these μ-ORs in the response enhancement following repeated Na+ challenge. Therefore, we used whole-cell recordings in acute brain slices to determine neuronal plasticity in the electrical properties of the MnPO Na+ sensor-specific neuronal population following multiple Na+ depletions. Our results show that the population of Na+ sensor neurons was represented by 80% of MnPO neurons after a single Na+ depletion and was reduced after three Na+ depletions. Interestingly, the subpopulation of Na+ sensors responding to D-Ala2,N-MePhe4,Gly-ol-enkephalin (DAMGO), a specific μ-OR agonist, represented 11% of MnPO neurons after a single Na+ depletion and the population doubled after three Na+ depletions. Moreover, Na+ sensor neurons displayed modifications in the discharge pattern distribution and shape of calcium action potentials after three Na+ depletions but these changes did not occur in Na+ sensors responding to DAMGO. Thus, the reinforced μ-OR functionality in Na+ sensors might take place to control the neuronal hyperexcitability and this plasticity in opioid-sensitive and Na+ detection MnPO networks might sustain the enhanced salt ingestion induced by repeated exposure to Na+ depletion.