The endogenous kappa agonist, dynorphin(1-13), does not alter basal or morphine-stimulated dopamine metabolism in the nigrostriatal pathway of the rat.

ABSTRACT

Dopaminergic pathways in the brain of the rat have been shown to possess both mu and delta opioid regulatory inputs. In contrast, studies with synthetic kappa opiate agonists have demonstrated a lack of regulation of these dopaminergic systems by kappa opioids. The present authors have extended these observations, to study the effects of the putative endogenous kappa agonists, dynorphin (1-13), on the metabolism of nigrostriatal dopamine in the rat after intraventricular administration. The stability of the intraventricularly administered dynorphin was confirmed in vivo by measuring corticosterone in plasma in the same animals utilized for neurochemical analyses. This is a neuroendocrine parameter which has been demonstrated to possess central regulation by independent mu and kappa receptors. While morphine given parenterally elevated both the level of corticosterone in plasma and the central metabolism of dopamine, neither the parenteral administration of the kappa agonist, U50488H, or the intraventricular administration of dynorphin altered central metabolism of dopamine. However, in both cases, levels of corticosterone in plasma were dramatically elevated, clearly demonstrating the bioavailability of the kappa agonists. The actions of morphine on the metabolism of dopamine, which can be antagonized by pretreatment with synthetic kappa agonists, were not antagonized by dynorphin(1-13). To summarize, the present data indicated that the nigrostriatal dopaminergic pathway in the rat lacks kappa opioid regulation. In addition, while synthetic kappa agonists also possessed mu antagonist actions, the endogenous ligand, dynorphin, did not.