The effect of LSD and 2-bromo LSD on the striatal DOPA accumulation after decarboxylase inhibition in rats.
LSD and BOL (0.125-0.5 mg/kg) were equipotent in increasing the in vivo tyrosine hydroxylation in the striatum as measured by the accumulation of DOPA after inhibition of neuronal decarboxylase. However, with 2--4 mg/kg doses, the maximum effect of BOL was larger than that of LSD. LSD and BOL antagonized the apomorphine-induced decrease of DOPA accumulation, without affecting the haloperidol-induced increase. LSD like apomorphine inhibited the increase of DOPA accumulation seen after reserpine, cerebral hemisection and after gamma-butyrolactone (GBL). The effect of apomorphine in rats given GBL was blocked by haloperidol, but not by BOL and promethazine, whereas that of LSD was inhibited by haloperidol, BOL, and promethazine. These findings suggest that LSD and BOL directly affect nigro-neostriatal dopamine neurons. LSD therefore appears to be a partial agonist and BOL a pure antagonist at dopamine autoreceptors. It is proposed in addition that LSD activates and BOL blocks 5-HT receptors that control DOPA formation.
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004295:Dihydroxyphenylalanine; D012110:Reserpine; D008238:Lysergic Acid Diethylamide; D006220:Haloperidol; D001058:Apomorphine; D015107:4-Butyrolactone