Effect of nicotine use and withdrawal on brain preproenkephalin A mRNA.
Although the effect of nicotine on brain neurotransmitters and behavior has been studied, the mechanism(s) by which nicotine contributes to tobacco use remains unclear. One transmitter that may relate to long-term nicotine use and its withdrawal is enkephalin, a five-amino acid opioid peptide derived from the proenkephalin A family. In the present study we determined the effect of acute and chronic nicotine treatment and its withdrawal on preproenkephalin A mRNA levels (PPE mRNA) in specific rat brain regions using Northern blot analysis. Acute treatment with nicotine produced a significant increase in PPE mRNA in striatum and hippocampus. Chronic treatment with nicotine caused a significant decrease in PPE mRNA in these brain regions. In both striatum and hippocampus there was a rebound increase in PPE mRNA 24 h after nicotine cessation which approached the saline level 7 days later. Nicotine withdrawal 24 h following nicotine cessation, caused a significant increase in PPE mRNA in both brain regions. These effects of nicotine were blocked by pretreating rats with the nicotinic antagonist, mecamylamine. These data strongly suggest that brain opioid system(s) are involved in mediating nicotinic responses and its withdrawal and may have clinical implications in treating nicotine addiction.
Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy and Tobacco and Health Research Institute, University of Kentucky, Lexington, KY 40536, USA. houdi@pop.uky.edu
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Houdi
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D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D014018:Tissue Distribution
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D009538:Nicotine; C033660:preproenkephalin