CHRONIC MORPHINE INCREASES CALBINDIN D-28K IN RAT STRIATUM - POSSIBLENMDA RECEPTOR INVOLVEMENT

THE neuronal intracellular calcium-binding protein calbindin D-28k is a neurochemical marker in the striatum. normally expressed in the matr ix compartment and absent from the mu-opiate receptor-enriched strioso mal (patch) compartment. Because chronic treatment with morphine has b een reported to increase calcium levels in synaptosomes of rat striatu m, we studied effects of morphine on calbindin immunoreactivity (ir) i n rat brain, using immunocytochemistry. Treatment with morphine for 5 days increased calbindin-ir in the striatal matrix, and induced intens e calbindin-ir in the patch compartment. Increased calbindin-ir in pat ches persisted through day 14 post-morphine. Co-administration of the NMDA receptor antagonist MK-801 blocked the morphine-induced increase in calbindin-ir in patches. We suggest that chronic morphine treatment may increase calcium and calbindin levels via increased glutamatergic transmission in striatum. These findings are consistent with reports that MK-801 inhibits tolerance to morphine, and provide a possible mec hanism and anatomical substrate for this inhibition.