Effect of nicotine on mRNA levels encoding opioid peptides, vasopressin and ?3 nicotinic receptor subunit in the rat

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Abstract
The effect of acute and chronic nicotine treatment of rats on the mRNA levels coding for the three opioid peptide precursors, for provasopressin and for the a3 subunit of nicotinic receptors in brain, pituitary and/or adrenal medulla of rats was investigated. Nicotine was found to increase the levels of proenkephalin mRNA in the adrenal medulla, but did not affect the levels of PENK mRNA in striatum, hypothalamus and hippocampus. The mRNA levels of prodynorphin were increased together with that of provasopressin in the hypothalamus after nicotine, whereas the prodynorphin mRNA levels in the hippocampus and the striatum remained unchanged. Nicotine treatment resulted in an increase in the pro-opiomelanocortin mRNA levels in the anterior pituitary and in a decrease in the intermediate pituitary, but did not change the levels of pro-opiomelanocortin mRNA in the hypothalamus. The levels of mRNA coding for the α3 subunit of nicotinic receptors in the hypothalamus and the adrenal medulla remained unchanged. The increase in the prodynorphin and provasopressin mRNA levels in the hypothalamus was most pronounced 1 day after s.c. application of two doses of 0.4 mg/kg nicotine (about 100% above control). A smaller increase in mRNA concentrations (about 30%) was found after tonic infusion of the drug for 4 days (4 mg/kg per day), whereas no change was observed after tonic infusion of nicotine for 7 and 14 days indicating the development of complete tolerance. The increase in proenkephalin mRNA levels in the adrenal medulla was highest after the short-term application of nicotine (about 150% above control). Less, but still significant increases in the mRNA levels (about 40%) were also seen after 7 and 14 days of tonic nicotine administration suggesting that no complete desensitization is developing to the effect of nicotine. This desensitization appeared to be less pronounced when the drug was applied in a pulsatile manner using minipumps, since a high increase in the PENK mRNA levels (100% above control levels) was observed after intermittent infusion of nicotine (six boli per day of 1 mg/kg for 7 days). These findings demonstrate that nicotine can alter gene expression of opioid peptides and vasopressin in certain rat tissues, and that the mode of drug administration plays an important role in this effect of nicotine. The possibility that the ‘pulsatile’ administration of nicotine by cigarette smokers may also result in an altered expression of opioid peptide genes in humans is discussed.