Chronic nicotine treatment changes differentially the effects of acute nicotine on the three main dopamine metabolites in mouse striatum.
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 degrees C, acute nicotine treatment induced marked hypothermia (-5.2 to -6.7 degrees C) in both chronic nicotine treated and control mice, an effect that was prevented by elevating the ambient temperature to 32-34 degrees 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 degrees 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 degrees 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Leikola-Pelho
T
T
Department of Pharmacy, University of Helsinki, Finland.
Heinämäki
J
J
Laakso
I
I
Ahtee
L
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003367:Cotinine / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006719:Homovanillic Acid / Q000378:metabolism; D000090023:Metallothionein 3; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*
D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D015102:3,4-Dihydroxyphenylacetic Acid; D009538:Nicotine; C001746:3-methoxytyramine; D003367:Cotinine; D004298:Dopamine; D006719:Homovanillic Acid