Regulation of calbindin-D28K gene expression in response to acute and chronic morphine administration

The effect of acute and chronic morphine administration on calbindin-D28K (calbindin) gene expression has been studied. One group of adult male rats received a single injection of morphine (10 mg/kg, s.c.) or saline and were sacrificed 1 or 4 h later. Another group was injected with escalating doses of morphine sulfate twice daily for 15 days to induce tolerance and physical dependence. Rats were sacrificed 1 h after the last injection. In a third group, the effect of naloxone-precipitated withdrawal on gene expression in morphine-addicted rats was also analyzed 1 h after naloxone (1 mg/kg, i.p.). The cerebellum and remaining brain (minus the cerebellum) were removed, and total RNA was extracted and used for analysis. Calbindin mRNA levels in cerebellum were decreased to 30%-40% control at 1 and 4 h after a single morphine injection. Co-administration of the opiate antagonist, naloxone, reversed the effect of morphine. Tolerance developed to the acute effects in that levels were not altered significantly 1 h after morphine injection in chronically-treated rats. Unlike the cerebellum, calbindin mRNA in the remainder of the brain (minus the cerebellum) was unchanged 1 and 4 h following morphine administration to drug-naive rats, but was increased more than 2-fold compared to controls 1 h after morphine injection in chronically treated animals. Naloxone-precipitated withdrawal caused a small (20%) but significant decrease in calbindin mRNA in the cerebellum, with no change in the brain (minus the cerebellum).(ABSTRACT TRUNCATED AT 250 WORDS)