Effect of l-tetrahydropalmatine on dopamine release and metabolism in the rat striatum.
In vivo voltammetric measurements of striatal extracellular DOPAC concentrations and of striatal DA release in combination with post-mortem analysis of striatal catechols were performed in the rat to study the effects on the nigro-striatal neurons of a Chinese neuroleptic, l-tetrahydropalmatine (l-THP), which is known to block post-synaptic dopaminergic receptors. l-THP injected at doses that cause sedation in rats and mice (5-10 mg/kg) induced a marked increase in post-mortem DOPAC levels (+250%), while no significant effect was observed on postmortem DA levels. The extracellular DOPAC concentration was increased to 155 +/- 9% of the control value after l-THP administration (1 mg/kg, IP). Further, an injection of l-THP (1 mg/kg, IP) induced an increase in extracellular DA concentration (220% of the basal value), reversed the decrease in extracellular DA concentration induced by apomorphine (0.05 mg/kg, SC) and enhanced the effects of the electrical stimulation of the nigro-striatal pathway. These results confirm that l-THP acts on the nigro-striatal neurons as a dopaminergic antagonist that can block both post- and presynaptic receptors.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001600:Berberine Alkaloids / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000032:analysis / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D004558:Electric Stimulation; D004563:Electrochemistry; D008297:Male; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects
D000470:Alkaloids; D001600:Berberine Alkaloids; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; C014215:tetrahydropalmatine; D004298:Dopamine