Nicotine Induces Opioid Peptide Gene Expression in Hypothalamus and Adrenal Medulla of Rats

Summary

Two consecutive injections of nicotine (0.4mg/kg; s.c.; 4 pm and 9 am) resulted in an more than twofold increase in the levels of mRNA coding for prodynorphin (PDYN) and for provaso- pressin in the hypothalamus of rats measured 21 hour after the first injection. In contrast, the levels of proenkephalin (PENK) and proopiomelanocortin (POMC) mRNAs in the hypothalamus remained unchanged. A much smaller increase (about 30%) in the level of PDYN mRNA was observed when nicotine (4 mg/kg/day; s.c.) was chronically applied via minipumps for 7 days. Moreover, PDYN mRNA levels returned to normal when the same dose of nicotine was continuously applied for 14 days indicating a complete desensitization to the effect of nicotine upon PDYN gene expression. Hypothalamic mRNA levels coding for the α ₃-subunit of the neural nicotinic receptors were unchanged suggesting no upregulation of the biosynthesis of this particular receptor subunit by nicotine. In the adrenal medulla, a pronounced increase in the PENK mRNA levels was observed (more than twofold) after two injections of nicotine. Moreover, PENK mRNA levels were still significantly elevated (by about 60%) when nicotine was tonically infused by minipumps (4 mg/kg/day) for 7 and 14 day indicating that the nicotinic receptors in the medulla are not completely desensitized by these treatments. A more effective induction of the PENK gene was obtained when nicotine was chronically applied in a pulsatile fashion via minipumps (6 mg/kg/day for 7 days; in 6 pulses/day).