Age-related changes in striatal dopamine D2 receptor binding in weaver mice and effects of ventral mesencephalic grafts

Dopamine (DA) D2 receptor binding is increased in the striatum of 5-6 months old weaver mutant mice (Kaseda et al. 1987). This may occur in response to the loss of DA neurons in the midbrain and the decrease in DA content in the striatum of homozygous mutants. One purpose of the present study was to determine if the diminished DA innervation is associated with changes in D2 receptors at earlier ages and if the increase in DA D2 receptor binding seen at 5-6 months is a lasting phenomenon. Specific [³H]spiperone binding was measured in the dorsolateral (DL), dorsomedial (DM) and ventrolateral (VL) striatum and in the nucleus accumbens (AC) of homozygous weaver mutant mice (wv/wv), heterozygous littermates (wv/+) and wild-type controls (+/+). Mice were studied at 20 days and 1, 3, 6, 9 and 12 months of age. The difference in specific [³H]spiperone binding in DL striatum between wv/wv and +/+ mice was significantly greater at 6 months than the difference at 1 month and at 12 months of age. Foetal ventral mesencephalic grafts survive and establish functional innervation in the striatum of weaver mice as shown by the induction of a contralateral turning bias (Low et al. 1987). The second aim of the present studies was to determine if such grafts would also reverse the increase in DA D2 receptor binding in the striatum. Aspiration cavities were prepared in the cortex of weaver mice, and ventral mesencephalic tissue from E14-E15 +/+ foetuses was subsequently placed on the surface of the right dorsal striatum when the recipients were 3 months old. At 6 months of age, specifie [³H]spiperone binding was determined in DM and DL striatum and in AC. Compared with the non-grafted side, the decreases in [³H]spiperone binding on the right (grafted) side in DL and DM striatum of the transplanted group were significantly greater than the differences in the other two groups. Since the grafts were introduced at an age (3 months) at which no significant difference in binding is seen between wv/wv and + / +, it appears that the grafts may prevent the increase in DA D2 receptor binding which is seen in non-grafted weaver mice at 6 months of age.