Dopamine synthesis in inbred mouse strains which differ in numbers of dopamine neurons

BALB/cJ and CBA/J mice have been shown to have different numbers of dopamine (DA) neurons in the central nervous system, with BALB/cJ mice having 20-50% more DA neurons in each dopaminergic cell group which is reflected in a difference in tyrosine hydroxylase activity in these cell groups. The present study compared the levels of DA and the rate of DA synthesis between these two inbred mouse strains. Three measures were used to reflect the rate of DA synthesis: the levels of DA metabolites (DOPAC and HVA) in the striatum, the rate of disappearance of DA following inhibition of tyrosine hydroxylase with alpha-methyl-P-tyrosine, and the rate of accumulation of DOPA following inhibition of aromatic amino acid decarboxylase with NSD-1015. Striatal DA levels were slightly higher in CBA/J mice than BALB/cJ mice. The rate of DA synthesis in the striatum, as estimated from the accumulation of DOPA following NSD-1015 injection or from the decline of DA levels following alpha-methyl-p-tyrosine injection, was from 30-50% greater in the BALB/cJ mice compared to the CBA/J mice. In striatum, DOPAC levels were higher, HVA levels lower, and DOPAC plus HVA levels equal in CBA/J mice compared to BALB/cJ mice. The results show that BALB/cJ mice, with more DA neurons than CBA mice, also synthesize more DA. In addition, the data suggest that DA levels do not necessarily reflect numbers of DA neurons, and that catecholamine metabolite levels are not a good measure for comparing catecholamine synthesis between inbred animal strains.