Different changes in striatal dopamine metabolism induced by nicotine in mice kept at different ambient temperatures. Evidence for partly separate metabolic routes of dopamine derived from separate compartmentations.

Abstract

Further information about the nicotine-induced changes in striatal dopamine metabolism in hypothermic mice was searched by measuring the contents of dopamine and its metabolites (3,4-dihydroxyphenylacetic acid, DOPAC; 3-methoxytyramine, 3-MT; and homovanillic acid, HVA) after blocking the synthesis of dopamine by alpha-methyl-p-tyrosine (alpha-MT). This method gave a possibility to study the effect of nicotine on the metabolism of dopamine in two pools (the cytoplasmic "newly-synthesized" dopamine and the granular dopamine). 3 mg/kg of (-)nicotine was given s.c. four times, at 110, 80, 50 and 20 min, and alpha-MT (250 mg/kg i.p.) at 60 min before sacrifice. To prevent the peripheral effects of nicotine all mice were given hexamethonium (10 mg/kg i.p.) at 140 min before sacrifice. Hexamethonium did not alter striatal dopamine metabolism. Experiments were performed at 20-22 degrees C at which temperature nicotine induced hypothermia or at 32-34 degrees C. The alpha-MT-induced proportional decrease of 3-MT content was clearly less than that of dopamine content. On the contrary the alpha-MT treatment decreased the DOPAC content proportionally more than the dopamine content. Thus DOPAC could not be solely formed from the same dopamine pool as 3-MT. These results indicate that 3-MT reflects best the metabolism of the granular dopamine and DOPAC that of the "newly-synthesized" dopamine. In hypothermic mice nicotine administration reduced the alpha-MT-induced depletion of the dopamine content.(ABSTRACT TRUNCATED AT 250 WORDS)