Dopamine deficiency in the weaver mutant mouse.

The dopamine system in weaver mutant mice (B6CBA-Aw-J/A background) was studied. Dopamine was 27% lower in the olfactory tubercle, 77% lower in the frontal cortex, and 75% lower in the striatum of 6-month-old weaver mice compared to control mice of the same age. Norepinephrine and serotonin were not lower in these brain areas. Tyrosine hydroxylase activity in the striatum was measured with a radiometric assay and was 70% lower in weaver mice. Examination of mice from 11 to 180 days of age revealed that the dopamine system failed to develop in weaver mice. Motor activity in individual animals was assessed using circular photocell activity cages with minimal illumination. Apomorphine and pergolide, direct dopamine agonists, increased activity more in weaver mice than in normal littermates. Amphetamine, which releases endogenous stores of dopamine, was less active in mutant mice. These findings provide suggestive evidence that postsynaptic dopamine receptors in weaver mutants might have become supersensitive as a result of lower levels of dopamine in motor areas of the brain. Anatomical evidence of dopamine system abnormalities was found in weaver mice by examination of serial sections cut from the midbrain of mutant and normal mice. The pars compacta of the substantia nigra in weaver mice appeared hypocellular when compared with the corresponding sections from controls. Fewer large neurons were seen in the affected animals. This study illustrates that weaver mice have specific deficiencies in the dopamine system. The weaver mouse might provide a way of examining the biochemical and behavioral effects of long term dopamine deficiency and a way to examine drugs to treat dopamine-deficient states in vivo.