CHRONIC MORPHINE DECREASES CALBINDIN D-28K IMMUNOREACTIVITY IN A SUBSET OF CEREBELLAR PURKINJE NEURONS OF RAT-BRAIN

Calbindin D-28k is an intracellular calcium binding protein that is ex pressed in the cell bodies, nuclei, dendrites, and axons of nearly all Purkinje neurons of the rat cerebellum. Acute morphine administration has been reported to decrease the level of calbindin mRNA in extracts of whole rat cerebellum [75]. Using immunocytochemistry, we studied t he effects of chronic morphine administration and morphine abstinence on levels of calbindin in cerebellar Purkinje neurons. Treatment of ma le rats for 5 days with either morphine injections (10 mg/kg s.c., twi ce daily) or subcutaneously implanted morphine pellets (75 mg/pellet, once daily) markedly decreased levels of calbindin immunoreactivity in long stretches of Purkinje cell bodies in various folia of cerebellum . After 7 days of abstinence from morphine, the number of calbindin-po sitive neurons was still significantly decreased, and at 14 days of ab stinence, the number of labeled neurons continued to be below that in control rat brain. The effects of morphine in cerebellum were not anta gonized by co-administration of the N-methyl-D-aspartate receptor anta gonist, MK-801 (0.2 mg/kg, twice daily for 5 days). MK-801 alone also decreased the number of calbindin-positive cells, but in a different p attern from that of morphine. Our findings of decreased calbindin immu noreactivity in Purkinje neurons following chronic morphine administra tion and abstinence suggest that persistent alterations in intracellul ar calcium buffering may be associated with opiate tolerance and depen dence in cerebellum.