PMID: 18197273Jan 17, 2008Paper

Chronic nicotine treatment induces rat CYP2D in the brain but not in the liver: an investigation of induction and time course

Journal of Psychiatry & Neuroscience : JPN
Jiang YueRachel F Tyndale

Abstract

CYP2D6 levels are higher in many brain regions of human smokers in comparison with nonsmokers. We have shown that CYP2D is expressed in rat brain regions and that enzyme activities correlate with protein and messenger ribonucleic acid (mRNA) levels. The aims of this study were to investigate whether nicotine can induce rat brain CYP2D, to determine the recovery time course of the induction and to investigate the mechanism of induction through measuring mRNA levels over time. Rats were either treated once with either saline or nicotine (1 mg base/kg, subcutaneous and sacrificed 8 hours after the treatment or treated daily for 7 days and sacrificed 0.5-24 hours after the last injection. The CYP2D protein and mRNA levels were assessed by immunoblotting, immunocytochemistry and slot blotting. There were no changes in brain CYP2D levels after a single nicotine injection. Following chronic nicotine treatment, levels were maximal at 8 hours and returned to control levels by 12 hours after nicotine treatment in all 3 regions assessed. At 8 hours after nicotine treatment, CYP2D levels were significantly (p < 0.05) higher than levels in saline-treated control animals in the cerebellum (1.4-fold), hippocampus (1.3-fold) and striatum (3.2-...Continue Reading

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