LONG-TERM EFFECT OF RU24722 ON TYROSINE-HYDROXYLASE IN THE RAT LOCUS-CERULEUS - DIFFERENTIAL-EFFECTS OF 2 ENANTIOMERIC FORMS

RU24722, as a racemic mixture, has been found to act on neuronal activ ity and the long term regulation of tyrosine hydroxylase in the locus coeruleus of the rat. In this study, the effects of two enantiomeric d erivatives of RU24722 (3alpha and 16alpha forms), as compared to the r acemic form itself, are studied. The short term effect was estimated 2 0 min after treatment by measuring variations in 3,4-dihydroxyphenylac etic acid content in the locus coeruleus. The long term effect was det ermined by evaluating tyrosine hydroxylase protein concentration in th e locus coeruleus 3 days after a single injection. Comparison of actio ns of both enantiomers showed that the 16alpha form was 3-fold more po tent in eliciting tyrosine hydroxylase protein elevations at three day s, whereas the 3alpha isomer increased 3,4-dihydroxyphenylacetic acid content 2-fold more in the short term. These results seem to show that the 16alpha configuration is crucial for the long term regulation of tyrosine hydroxylase protein elicited by RU24722 within the locus coer uleus.