Centrally-administered opioid selective agonists inhibit drinking in the rat

The effects of intracerebroventricular injection of mu (morphine), kappa (dynorphin-(1–13), ethylketocyclazocine, and U50,488H), and delta ([D-Pen 2,D-Pen 5]enkephalin) opioid agonists on water intake of 14 hr water deprived rats was studied. All agonists caused a dose related decrease in time spent drinking, with a rank order potency of dynorphin-(1–13) > morphine > ethylketocyclazocine >[D-Pen 2,D-Pen 5]enkephalin = U50,488H. With the exception of morphine, all of the compounds increased the latency to begin drinking, but only at the highest doses tested. The rank order potency for this endpoint was dynorphin-(1–13) = ethylketocyclazocine > [D-Pen 2,D-Pen 5]enkephalin > U503, 488H. The potent inhibition of drinking following centrally-given dynorphin-(1–13), at doses that did not affect the latency to begin drinking, supports a role for endogenous dynorphin in the homeostatic control of water balance. This function may not be primarily mediated through activation of a kappa opioid receptor since dynorphin-(1–13) was 80–230 times more potent than the selective kappa agonist, U50,488H or ethylketocyclazocine.