Effect of imipramine on central 5-hydroxytryptamine turnover and metabolism in rats.

The levels of [3H]-5-HT and [3H]-5-HIAA in P2-fraction from rats treated with a single dose of imipramine were lower at 2, 5 and 10 min after intraventricular administration of [3H]-5-HT, compared with control animals, though these levels were statistically insignificant. Thereafter, however, the values became higher than in the controls. After long-term administration of imipramine, the levels of [3H]-5-HT and [3H]-5-HIAA in P2-fraction were, at any time after intraventricular administration of [3H]-5-HT, significantly lower than those in the fraction from controls. The endogenous contents of tryptophan and 5-HIAA were not altered either with a single dose or by long-term administration of imipramine, however, the content of endogenous 5-HT was decreased by long-term administration of imipramine. These results indicate that the rate of disappearance of 5-HT from presynaptic neurons was accelerated by long-term administration of imipramine.