Relation between brain dopamine loss and D2 dopamine receptor density in MPTP monkeys

The relationship between dopamine (DA), dihydroxyphenylacetic acid (DOPAC) or homovanillic acid (HVA) concentrations and [3H]spiperone binding to D2 DA receptors in caudate nucleus, putamen and nucleus accumbens following DAergic lesion with MPTP in monkeys was investigated. The level of DA depletion varied from 37% to 100% while a mean elevation in [3H]spiperone binding density of 114.8 +/- 4.7% of control (P less than 0.01) was observed when DA depletion was at least 90% of control values. A logarithmic correlation (y = -7.19 In x +111.15; r = -0.54, P less than 0.01) between DA concentrations (x) and the density of [3H]spiperone binding sites (y) was observed in all brain regions. The correlation between DOPAC or HVA concentrations and [3H]spiperone binding was best represented by linear rather than logarithmic equations. These results indicate that supersensitivity of DA receptors develops after MPTP lesion in monkeys when the number of remaining nerve fibers becomes too few to compensate for the DA loss.