Interaction of haloperidol and gamma-butyrolactone with (+)-amphetamine-induced changes in monoamine synthesis and metabolism in rat brain.
The interaction of (+)-amphetamine with haloperidol and gamma-butyrolactone on synthesis of monoamines in rat brain regions was investigated using an in vivo method, in which the accumulation of dopa and 5-hydroxytryptophan (5-HTP) was measured after inhibition of the aromatic amino acid decarboxylase by means of 3-hydroxybenzylhydrazine. The accumulation of 3-methoxytyramine (3-MT) after inhibition of the monoamine oxidase with pargyline was taken as an indicator of the in vivo release of dopamine (DA) into the extraneuronal space. (+)-Amphetamine at doses of 1--3 mg/kg caused an increase of dopa formation in the DA-rich areas c. striatum and mesolimbic forebrain but had no effect on dopa formation in neocortex and 5-HTP formation in all brain regions investigated. At a dose of 10 mg/kg (+)-amphetamine decreased dopa as well as 5-HTP formation in all brain regions studied. 3-MT accumulation in whole rat brain was stimulated by (+)-amphetamine as well as haloperidol and inhibited by gamma-butyrolactone. Combined treatment with haloperidol and (+)-amphetamine not only potentiated the stimulation of dopa formation but also the increase of 3-MT accumulation. Pretreatment with gamma-butyrolactone antagonized the stimulation of 3-MT formation induced by (+)-amphetamine at a dose of 10 mg/kg. This dose of (+)-amphetamine markedly counteracted the gamma-butyrolactone-induced increase in dopa formation especially in the DA-rich areas. The data support the view that impulse flow in DA neurons facilitates the effect of (+)-amphetamine on DA release and DA synthesis. Inhibition of catecholamine synthesis after high doses of (+)-amphetamine may be due to an increase in cytoplasmatic DA concentration causing end-product inhibition of tyrosine hydroxylase.
D015107:4-Butyrolactone / Q000494:pharmacology*; D006916:5-Hydroxytryptophan / Q000096:biosynthesis; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004347:Drug Interactions; D005663:Furans / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D008032:Limbic System / Q000378:metabolism; D008297:Male; D051381:Rats; D014439:Tyramine / Q000378:metabolism
D001679:Biogenic Amines; D005663:Furans; D004295:Dihydroxyphenylalanine; D006916:5-Hydroxytryptophan; D000661:Amphetamine; D006220:Haloperidol; D015107:4-Butyrolactone; D014439:Tyramine