LONG-TERM EFFECT OF RU24722 ON TYROSINE-HYDROXYLASE PROTEIN-CONCENTRATION IN THE LOCUS-COERULEUS OF MICE - DIFFERENTIAL RESULTS IN BALB/C, C57BL/6 AND THEIR CB6-F1 HYBRID

The long term effect of RU24722 (14,15-dihydro-eburnamine-14-OL) on tyrosine hydroxylase of noradrenergic locus coeruleus neurons have been studied in Balb/C and C57BL/6 mice strains and their CB6 F1 hybrids. Mice were treated with a single i.p. injection of increased doses of RU24722 and a time-course was performed at 20 mg/kg. Under steady-state conditions, the parental strains presented a significantly different tyrosine hydroxylase concentration, which appeared to be dominantly transmitted to the F1 hybrid. After treatment by RU24722, a long term change in tyrosine hydroxylase protein concentration in the locus coeruleus of each strain was observed. The strain Balb/C presented a greater reactivity for RU24722 than the strain C57BL/6 and F1 hybrids: the reactivity for the inducer could also be dominantly transmitted. The concentration of tyrosine hydroxylase at the maximal effect of the inducer (3 days after a simple injection of 20 mg/kg of RU24722) was similar in the two inbred strains and their F1 hybrid. But the increase of the enzyme concentration appeared to be in inverse relation to its initial level in the three strains. It is hypothesized that the induction of tyrosine hydroxylase could be limited by a superior threshold possibly due to a retro-inhibition of the enzyme on its own synthesis.