[Suppressive effects of lisuride on the synthesis, release and metabolism of dopamine in rat brain].
Effects of lisuride, a central dopaminergic agonist of the ergot type, on the biosynthesis, release and metabolism of dopamine at the dopaminergic nerve terminals of the rat brain were studied under several experimental conditions. 1) In the rat whose impulse flow of dopamine neurons and the activity of aromatic amino acid decarboxylase were inhibited by the pretreatment with gamma-butyrolactone and with 3-hydroxybenzylhydrazine (NDS 1015), respectively, DOPA formation in the neostriatum and limbic forebrain were decreased significantly by the s.c. administration of lisuride at the dosage known to be ineffective on the postsynaptic dopamine receptor. 2) When it was measured by the accumulation of 3-methoxytyramine in the neostriatum and limbic forebrain of pargyline (MAO inhibitor)-pretreated rats, lisuride at the low dosage caused the inhibition of not only the spontaneous release of dopamine from the nerve terminal to the synaptic cleft, but also the release induced with methamphetamine. 3) In the rat whose dopamine biosynthesis was inhibited with alpha-methyl-p-tyrosine, lisuride caused the suppression of dopamine metabolism, resulting in significant increases of dopamine histofluorescence in the nucleus caudatus, olfactory tubercle and median eminence. As to the effect on dopamine histofluorescence, apomorphine at 1 mg/kg was equipotent to lisuride at 50 micrograms/kg. It was concluded from these results that lisuride administered at low dosage interacts preferentially with the presynaptic dopamine receptor, hereby causing the suppressive effects on the tyrosine hydroxylase reaction and the dopamine release mechanism in the dopamine nerve terminals of the brain.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003864:Depression, Chemical; D004088:Dihydroergotoxine / Q000494:pharmacology; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006651:Histocytochemistry; D006719:Homovanillic Acid / Q000096:biosynthesis; D008090:Lisuride / Q000494:pharmacology*; D008787:Metoclopramide / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism; D051381:Rats; D013469:Sulpiride / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004873:Ergolines; D004088:Dihydroergotoxine; D013469:Sulpiride; D008090:Lisuride; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D008787:Metoclopramide; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid