β-Endorphinergic system involvement in the inhibitory action of clonidine on induced sodium appetite

In the present study, we investigated the degree to which β-endorphin plays a role in the alpha 2-adrenergic/imidazoline receptor agonist attenuation of salt appetite. In order to evaluate whether the inhibitory action of clonidine (an α2-adrenergic/imidazoline receptor agonist) on induced sodium intake is mediated by the β-endorphinergic system, we used a β-endorphin deficient mouse line. β-endorphin knockout (βend(-/-)), heterozygous (βend(+/-)) and wild-type (βend(+/+)) mice were submitted to acute sodium depletion by a combined treatment of furosemide and low sodium diet and, 20h later, were administered with clonidine (0.5mg/kg). An hour later, the animals were subjected to a two-bottle choice test (water/2% NaCl). The results indicate that clonidine administration during the first stage of the test exerts an equivalent inhibition on sodium intake regardless of the genotype; however, in the final stage of the test, a reversal of the inhibitory response on induced sodium appetite becomes evident in the mice lacking β-endorphin. Moreover no differences in dipsogenic response were observed between the genotypes. Considering these results and the fact that plasma half-life of clonidine at the dose administered is approximately 3h, it is possible to speculate that the inhibitory effect of clonidine on sodium appetite may be independent of β-endorphin modulation during the first stage; however, the long-lasting inhibitory effect of clonidine may be mediated by the β-endorphinergic system. This evidence supports the existence of adrenergic and β-endorphinergic system interaction in the osmoregulatory response to achieve sodium balance.