CHRONIC ADMINISTRATION OF MORPHINE DECREASES LEVEL OF DYNORPHIN-A IN THE RAT NUCLEUS-ACCUMBENS

The effect of chronically administered morphine on the levels of dynor phin A in distinct regions of the brain (including medial frontal cort ex, 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 perio d of 5 days. The concentration of peptide was probed by radioimmunoass ay, following pre-separation of tissue extracts by reversed phase sepa ration on a SepPak C-18 cartridge. The result showed that the level of dynorphin A remained unaltered in all regions studied immediately bef ore (tolerance) and 20 hr after (withdrawal) the pump was removed. A s ignificant decrease in the level of dynorphin was found in the n. accu mbens 48 hr (abstinence) after removal of the pump. It is suggested th at previously observed changes in the reward system during abstinence may be connected with dynorphinergic neurones in the limbic system.