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)
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.
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Tirumalai
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Howells
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D064092:Calbindin 1; D064026:Calbindins; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis* / Q000235:genetics
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D009270:Naloxone; D009020:Morphine