Norepinephrine (NE) metabolism in brain regions was studied in the Purkinje cell 
degeneration (pcd) mutant mouse. The Purkinje cells, which are target cells for 
noradrenergic (NA) neurons, degenerate completely in the pcd mutant mouse 
between 17 and 45 days of age, but the NA terminals remain intact. The purpose 
of this study was to determine if cerebellar NE turnover is altered after 
Purkinje cell loss. The concentrations of NE and of its major metabolite in 
mouse brain, 3-methoxy-4-hydroxy-phenylglycol (MHPG) were measured by liquid 
chromatography with electrochemical detection. The concentration of MHPG and the 
concentration ratio MHPG/NE were taken as indices of NE turnover. Although the 
cerebellar content of NE in the pcd mice was not different from control mice, 
MHPG and the ratio MHPG/NE were decreased slightly in 3-month old, and more in 6 
and 9-month old, mutants compared to controls. No decrease in MHPG content or in 
the MHPG/NE ratio was detectable in younger mutants (22 or 45-day old). The 
accumulation of dopa (3,4-dihydroxyphenylalanine) after administration of NSD 
1015 to inhibit aromatic l-amino acid decarboxylase was determined as an index 
of NE synthesis. Dopa accumulation was decreased in cerebellum to 69%, 53% and 
37% of control values, respectively, at 3, 6 and 12 months in pcd mice, but was 
not changed in brain stem and was only slightly decreased in hypothalamus. No 
decrease in MHPG (content or concentration) or in the ratio MHPG/NE was found in 
brain stem. In hypothalamus, NE concentration and content were slightly 
increased in pcd mice at all ages, and the ratio MHPG/NE was decreased in 6 and 
9-month old mice. We conclude that although NA axons in the cerebellum are 
maintained in pcd mice after Purkinje cell degeneration, NE turnover is 
decreased, suggesting that the synthesis and release of neurotransmitter does 
not continue at normal rates when the target cells have degenerated.