Kappa-opioid receptors ( Kappa OR) are positioned to modulate pre- and post-synaptic responses of norepinephrine-containing neurons in the rat locus coeruleus (LC). The ability of an acute systemic injection of a long acting Kappa OR agonist, U50,488, to induce trafficking of Kappa OR was assessed in the LC using immunogold-silver detection in male Sprague-Dawley rats. U50,488 administration shifted immunogold-silver labeling indicative of Kappa OR from primarily plasmalemmal sites to intracellular sites when compared to vehicle-treated subjects. This translocation from the plasma membrane to the cytoplasmic compartment was prevented by pre-treatment with the Kappa OR antagonist, norbinaltorphimine (norBNI). To determine whether agonist stimulation could induce adaptations in the expression of the noradrenergic synthesizing enzyme, dopamine beta hydroxylase (DbH), and Kappa OR expression, Western blot analysis was used to compare expression levels of DbH and Kappa OR following U50,488 administration. Expression levels for DbH and Kappa OR were significantly increased following U50,488 administration when compared to controls. These data indicate that a systemic injection of a Kappa OR agonist stimulates internalization of Kappa ORs in noradrenergic neurons and can impact Kappa OR and DbH expression levels in this stress-sensitive brain region.