Effects of Short‐ and Long‐Term Protriptyline Treatment on Phospholipid Metabolism in Rat Brain

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Abstract
Wistar rats were injected i.p. with 10 mg/kg of protriptyline according to 1 of the following schedules: a single dose or daily for 4 days (short-term), or daily for 2 or 13 wk (long-term). Total lipid, total phospholipid and individual phospholipid contents in the brain were determined. The incorporation of 32P into individual phospholipids in vivo and the fatty acid composition of phosphatidylethanolamine in the brains of rats treated with protriptyline for 13 wk were studied. Three alternative phases of changes of total and individual phospholipid contents in the brain during 13 wk of experimentation were distinguished. An increase of phospholipid contents after 4 days, a decrease after 2 wk and a further increase after 13 wk of protriptyline administration were found. Phosphatidylinositol and phosphatidic acid levels after 13 wk of protriptyline administration were diminished. The decrease of specific radioactivity of phosphatidylethanolamine, phosphatidylcholine and phosphatidyolserine and the increase of phosphatidylinositol, phosphatidic acid and sphingomyelin in rats treated with the drug for a longer period of time were noted. No greater differences in fatty acid composition of phosphatidylethanolamine in the brains of the same group of rats were observed as compared to control. During long-term treatment with protriptyline the contents of lipids and phospholipids in rat brain are altered. The modification of the biological function of phospholipids in brain cell membranes is suggested.