Feed-back regulation of presynaptic D2 receptors blockaded by l-stepholidine and l-tetrahydropalmatine

The activity of tyrosine hydroxylase by accumulation of L-dopa content in the striatum under decarboxylase inhibitor (benserazide, 400 mg.kg-1) was measured by HPLC-ECD to ascertain whether l-SPD possesses an agonistic or antagonistic effect on D2 receptor subtype. The accumulated L-dopa content was increased with 1,4-butyrolactone (BL, 750 mg.kg-1) to 1.8 +/- s 0.6 micrograms.g-1 in rat striatum. After the rats were ip l-SPD 5 mg.kg-1 or l-tetrahydropalmatine (l-THP) 10-20 mg.kg-1, the increment of L-dopa level was much more than that in the BL group (P < 0.01) in a dose related manner. On the contrary, apomorphine (ip 5 mg.kg-1) abolished the accumulation of L-dopa induced by BL. Furthermore, l-SPD and l-THP not only reversed the negative feed-back regulation by apomorphine on the accumulated level of L-dopa, but also increased this level over the accumulation by BL. These results showed that l-SPD and l-THP do possess the antagonistic effect on presynaptic DA receptor (D2) without agonistic effect.