The transport and turnover of phospholipids in the rat nigrostriatal system: Effects of d-amphetamine and haloperidol

The nigrostriatal transport of phospholipids was studied using [³H]glycerol, ³²Pi and [³H]choline. [³H]glycerol was rapidly incorporated into phospholipid and significant amounts of labelled phospholipid were found in the striatum one hour after injection into the substantia nigra. In contrast, both ³²Pi and [³H]choline were more slowly incorporated into phospholipid and significant amounts of labelled phospholipid were not found in the striatum until 24 hours after injection. Once incorporated into the striatum, the [³H-glycerol] phospholipids showed both a rapid (t 1/2 = 1-4 days) and a slow (t 1/2 = 14 + days) turnover component while the [³²P] and [³H-Ch] phospholipids showed only a slow turnover component. The subcellular distribution of the rapidly transported [³H-glycerol] phospholipids was studied. Only [³H] phosphatidylcholine (PC) was specifically enriched in the synaptic membrane fraction. The hypothesis was tested that an increase in vesicular lysophosphatidylcholine (LPC) content is associated with dopamine (DA) release. The DA containing vesicles in the striatum were labelled by the intranigral injection of [³H] choline; seven days later, the animals were administered haloperidol to stimulate firing of the nigral-striatal DA neurons. Haloperidol significantly decreased rather than increased the [³H]LPC/[³H]PC ratio. The hypothesis was tested that chronic amphetamine treatment would inhibit phospholipid transport as a result of the decrease in neuronal activity. Chronic d-amphetamine treatment was found to have no effect on the fast component of [³H-glycerol] phospholipid turnover.