Summary
The effect of chronic treatment with nicotine on striatal dopamine metabolism was studied in mice by measuring the striatal concentrations of dopamine and its metabolites 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). (−)-Nicotine was administered for 7 days using subcutaneously implanted nicotine releasing reservoirs. The release of nicotine was confirmed by measuring nicotine and cotinine concentrations in the plasma. To study the possible tolerance induced by chronic nicotine treatment, acute challenge doses of (−)-nicotine (either 3 mg/kg given once or 1 mg/kg repeated 4 times at 30 min intervals) were given to mice on the 7th day after the implantation. At an ambient temperature of 20–22°C, acute nicotine treatment induced marked hypothermia (−5.2 to −6.7°C) in both chronic nicotine treated and control mice, an effect that was prevented by elevating the ambient temperature to 32–34°C.
Chronic nicotine treatment did not per se alter striatal dopamine metabolism. Acute nicotine administration altered the striatal dopamine metabolism in a temperature-dependent manner. In mice kept at 20–22°C, the DOPAC concentration rose slightly but concentrations of 3-MT and HVA fell, indicating a decrease in the release of dopamine. In contrast, in mice kept at 32–34°C the DOPAC and HVA concentrations were clearly elevated by acute nicotine, whereas the concentration of 3-MT was not altered. In these normothermic mice chronic nicotine pretreatment did not alter the effects induced by acutely administered nicotine. However, in mice kept at 20–22°C, chronic nicotine markedly enhanced the decrease in striatal HVA induced by the acute nicotine challenge although it did not further decrease 3-MT. Furthermore, the chronic pretreatment reversed the effect of acute nicotine on DOPAC in the hypothermic mice, so that the DOPAC concentration clearly fell instead of increasing. Since chronic pretreatment with nicotine changed the effect of acute nicotine on striatal DOPAC but not on 3-MT, the nicotinic cholinoceptors involved in the regulation of the intraneuronal dopamine metabolism (to DOPAC) and of impulse-mediated dopamine release (as reflected in 3-MT) differ from each other at least in their response to chronic nicotine administration.
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Leikola-Pelho, T., Heinämäki, J., Laakso, I. et al. Chronic nicotine treatment changes differentially the effects of acute nicotine on the three main dopamine metabolites in mouse striatum. Naunyn-Schmiedeberg's Arch Pharmacol 342, 400–406 (1990). https://doi.org/10.1007/BF00169456
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DOI: https://doi.org/10.1007/BF00169456