Differential time course of the effects of kappa-opioid agonist treatment on dynorphin A and on k-opioid receptor density

The effects of kappa-opioid agonist treatment on kappa-opioid receptor density and on dynorphin A levels in the rat brain were studied. Rats were treated with the selective kappa-opioid agonist U-69593 or vehicle for 5 d. Dynorphin A levels and kappa-opioid receptor binding were measured on day 8 (3 d after the last injection) or 22 (17 d after the last injection). On day 8, kappa-opioid receptor density was increased in the hypothalamus of rats treated with U-69593; there were no changes in the frontal cortex or caudate putamen. In contrast, there was an increase in dynorphin A levels in the frontal cortex and no changes in hypothalamus and caudate putamen in response to U-69593. On day 22, Bmax was decreased in frontal cortex and caudate putamen of U-69593-treated rats, whereas dynorphin A levels were increased in the caudate putamen and in the frontal cortex. These findings suggest that kappa-opioid receptor agonist treatment has long-term, continually changing effects on the kappa-opioid system.