H. Stephen Beyer

Induction and Desensitization of the c-Fos mRNA Response to Nicotine in Rat Brain.

Early rapid response genes such as c-fos are activated in the central nervous system by a variety of agents including psychostimulants. In the present studies, we investigated changes in c-fos mRNA content in several brain regions of the rat in response to nicotine. A single injection of nicotine ip increased the c-fos mRNA content within 30 min and returned toward baseline by 120 min. Significant elevations were induced by 0.5 mg/kg bw nicotine in the medial habenula and by 1.0 mg/kg in the hippocampus, dentate gyrus, and piriform cortex. At 1.0 mg/kg, significantly greater increases in c-fos mRNA levels were present in medial habenula and hippocampus compared to dentate gyrus and in dentate gyrus compared to piriform cortex. Moreover, at 1.0 mg/kg nicotine, increases were significantly less in cerebellar cortex and cingulate gyrus, and these were not dose-dependent. Mecamylamine, a nicotinic cholinergic receptor antagonist, significantly attenuated or eliminated c-fos mRNA response to 1.5 mg/kg nicotine in all regions, except in the cerebellar cortex. Desensitization of the c-fos mRNA response to nicotine was investigated by administering two injections of 2.0 mg/kg nicotine 2 h apart. In the hippocampus, dentate gyrus, and piriform cortex, the first dose of nicotine significantly reduced the c-fos mRNA response to a second dose. The magnitude of desensitization ranged from 43% (piriform cortex) to 81% (hippocampus). In summary, nicotine rapidly elevated the c-fos mRNA content in several rat brain regions. The sensitivity of this response to nicotine and development of desensitization differed among the regions.

Effect of food intake on the activity of liver enzymes in partially hepatectomized rats treated with tumor necrosis factor

After partial hepatectomy (PHx), there are significant changes in the activity of a number of enzymes in the regenerating rat liver. Administration of low doses of recombinant human tumor necrosis factor-alpha (rHu-TNF) to normal rats induces similar changes in some of the enzymes but not in others. Because certain observations suggest that TNF may play a dominant role in liver regeneration, we speculated that the discrepancies in enzyme activities may be due to the decrease in food intake caused by PHx. Accordingly, the activities of eleven liver enzymes of 70% PHx rats additionally treated i.p. with rHu-TNF (20-50 micrograms/kg/day for 3-4 days) were compared with those of (i) PHx controls fed ad lib., and (ii) PHx controls pair-fed the same amount of food. When pair-fed controls were used, the discrepancies in the activities of the enzymes that are affected by fasting tended to disappear, suggesting that the decrease in the food intake was responsible for the differences.

An analysis of total RNA translation products of rat liver during regeneration with a comparison to fetal liver.

We explored differences in the mRNA populations of regenerating, sham-operated, and fetal rat liver using two-dimensional gel electrophoresis to resolve the radiolabeled protein products of liver total RNA translated in vitro. Twenty-four translation products were changed significantly after partial hepatectomy and sham hepatectomy. Nine of the 24 products changed after partial hepatectomy only, while the remainder also changed after sham hepatectomy. Two of the nine increased during regeneration to relative levels similar to those found in fetal liver. However, substantial differences also exist between the translation products of regenerating and fetal liver. These results suggest that the response to partial hepatectomy involves the alteration of mRNAs present in normal liver and that this response does not duplicate the fetal pattern of hepatic total RNA translation activity.