Catecholamine synthesis in rat brain after axotomy: interaction between apomorphine and haloperidol.
Axotomy of the ascending monoaminergic fibers by means of a complete cerebral hemitransection stimulated the formation of dopa during 30 min after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCl, 100 mg/kg i.p., in c. striatum and the dopamine-rich part of the limbic system. Apomorphine, 0.5 mg/kg i.p., antagonized the accumulation of dopa not only on the intact but also on the lesioned side. Haloperidol, 2 mg/kg i.p., stimulated dopa accumulation on the intact side but could not further stimulate the increase in dopa caused by transection. When both drugs were given together, the inhibitory effect of apomorphine was fully counteracted by haloperidol on both sides. In the predominantly noradrenaline-innervated occipito-temporal cortex dopa formation was slightly higher on the lesioned than on the intact side and was not markedly influenced by apomorphine. In the rest of the hemispheres the apomorphine-induced decrease in  dopa formation was more pronounced on the intact than on the lesioned side and was fully antagonized by haloperidol. The dopamine concentration was slightly higher in the lesioned c. striatum as compared to the intact side irrespective of the drugs administered. In c. striatum and the limbic system haloperidol caused a decrease in dopamine on the intact side which was not antagonized by additional treatment with apomorphine. Hemitransection caused a decrease in noradrenaline especially in the hemisphere portion. Neither apomorphine nor haloperidol or both drugs in combination changed the latter effect. In general, the tyrosine concentration tended to be higher on the lesioned than on the  intact side in all brain structures investigated. The data support the view that a local receptor-mediated feedback mechanism exists which is controlling dopamine synthesis even in the absence of impulse flow.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004298:Dopamine / Q000096:biosynthesis; D004347:Drug Interactions; D005246:Feedback; D006220:Haloperidol / Q000494:pharmacology*; D008032:Limbic System / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000096:biosynthesis; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology; D009435:Synaptic Transmission; D014443:Tyrosine / Q000378:metabolism
D002395:Catecholamines; D011941:Receptors, Adrenergic; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine; D009638:Norepinephrine