Enkephalinergic mechanisms in the "compensated" phase of Parkinson's disease

Loss of 70-80% of striatal dopamine (DA) content has been regarded crucial to the onset of Parkinson's Disease (PD) (Bernheimer et al., 1973). Several compensatory mechanisms have been shown to develop in the nigrostriatal DA system which could possibly contribute to the maintenance of DA-ergic transmission at the early stages of the disease. Hornykiewicz (1966) proposed that the preclinical phase of Parkinsonism might be due to compensatory changes that permit residual DA-ergic neurons to subserve functions previously carried out by the entire nigrostriatal projection. One such compensatory mechanism may include increase in transmitter release from the remaining DA-ergic terminals (Agid et al., 1973), increase in the density of the biosynthetic enzymes of DA synthesis (Zigmond et al., 1984), and increase in the number of the D2 DA postsynaptic receptors (Bokobza et al., 1984). However, with further progression of striatal DA loss, these compensatory mechanisms become insufficient in maintaining adequate DA-ergic transmission and the clinical symptoms of the disease become apparent.