Chronic administration of morphine decreases level of dynorphin A in the rat nucleus accumbens.

Abstract The effect of chronically administered morphine on the levels of dynorphin A in distinct regions of the brain (including medial frontal cortex, olfactory tubercule, nucleus accumbens, dorsal and medial striatum), was determined in male Sprague-Dawley rats. The drug was delivered through a subcutaneously implanted Azlet miniosmotic pump over a period of 5 days. The concentration of peptide was probed by radioimmunoassay, following pre-separation of tissue extracts by reversed phase separation on a SepPak C-18 cartridge. The result showed that the level of dynorphin A remained unaltered in all regions studied immediately before (tolerance) and 20 hr after (withdrawal) the pump was removed. A significant decrease in the level of dynorphin was found in the n. accumbens 48 hr (abstinence) after removal of the pump. It is suggested that previously observed changes in the reward system during abstinence may be connected with dynorphinergic neurones in the limbic system.