EFFECT OF NICOTINE USE AND WITHDRAWAL ON BRAIN PREPROENKEPHALIN-A MESSENGER-RNA

Although the effect of nicotine on brain neurotransmitters and behavio r has been studied, the mechanism(s) by which nicotine contributes to tobacco use remains unclear. One transmitter that may relate to long-t erm nicotine use and its withdrawal is enkephalin, a five-amino acid o pioid 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 sp ecific 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 hip pocampus there was a rebound increase in PPE mRNA 24 h after nicotine cessation which approached the saline level 7 days later. Nicotine wit hdrawal 24 h following nicotine cessation, caused a significant increa se in PPE mRNA in both brain regions. These effects of nicotine were b locked 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 clin ical implications in treating nicotine addiction. (C) 1998 Elsevier Sc ience B.V. All rights reserved.