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We report here that the pattern of loss of dopamine that occurs in the brains of adult mice carrying the autosomal recessive weaver gene is the consequence both of failed postnatal development of the dopamine- containing mesostriatal innervation and of the disappearance of the early forming dopamine-island system. For these studies, we compared the contents of dopamine extracted from 3 divisions of the striatum, the caudoputamen, nucleus accumbens, and olfactory tubercle, and from the midbrain of weaver and control littermate pups. Catecholamines were extracted from tissues dissected from serial brain slices and were separated and measured using high-performance liquid chromatography followed by electrochemical detection. The anatomical pattern formed by the catecholamine-containing innervation of the developing striatum was studied in 8-, 11-, 20-d-old, and 1.5-month-old weaver and control mice using tyrosine hydroxylase immunohistochemistry. In weaver neonates (7- 8 d old), the dopamine-containing innervation of the caudoputamen is characterized by near-normal concentrations of dopamine and by a normal anatomical arrangement of dopamine islands. Subsequently, however, the weaver disease is expressed in the caudoputamen as a failure of the dopamine islands to persist and of the dopamine-containing innervation of the matrix to develop at a normal rate. Whereas the concentration of dopamine increases 4.4-fold between days 7 and 33 in normal animals, it increases only 1.6-fold in the weaver. In spite of the severe reduction of dopamine, the weaver's caudoputamen grows to near-normal size (85%).(ABSTRACT TRUNCATED AT 250 WORDS)

The postnatal development of the dopamine-containing innervation of dorsal and ventral striatum: effects of the weaver gene