Effect of (+) amphetamine on monoamine synthesis and metabolism after axotomy in rat forebrain.
(+)Amphetamine is known to produce feedback inhibition of catecholamine-containing neurons in the central nervous system due to its indirect receptor stimulating properties. This feedback control may involve postsynaptic receptors and neuronal loops or presynaptic receptors and may be restricted to the catecholaminergic terminal system. In order to study the effect of (+)amphetamine on catecholamine synthesis and metabolism in the terminal system changes in impulse flow were eliminated by cutting the ascending monaminergic axons. Axotomy of the ascending monominergic fibers by means of a complete transverse cerebral hemisection resulted in a 3-fold increase in Dopa formation in the lesioned forebrain during 30 min after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCl, 100 mg/kg i.p. (+)-Amphetamine sulfate, 10 mg/kg i.p. antagonized the hemisection-induced increase in Dopa formation and reduced the formation of 5-hydroxytryptophan. Pretreatment with haloperidol, 5 mg/kg i.p. failed to counteract the effect of (+)amphetamine. In the intact forebrain the stimulation of Dopa accumulation was more than additive after combined treatment with haloperidol and (+)amphetamine. Hemitransection retarded the disappearance of dopamine and noradrenaline after administration of alpha-methyl-p-tyrosine methylester HCl,300 mg/kg. (+)-Amphetamine, 10 mg/kg accelerated the utilization of dopamine on the lesioned side. Hemitransection reduced the formation of 3-methoxytyramine during 1 h after pargyline, 75 mg/kg i.p. After (+)amphetamine 3-methoxytyramine formation in the intact forebrain was 3 times higher than in the lesioned forebrain. The action of (+)amphetamine on dopamine synthesis and release appears to be dependent on the firing rate in dopamine neurons.
D006916:5-Hydroxytryptophan / Q000096:biosynthesis; D000818:Animals; D001369:Axons / Q000502:physiology*; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003714:Denervation; D003913:Dextroamphetamine / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism; D005246:Feedback; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D014364:Tryptophan / Q000378:metabolism; D014439:Tyramine / Q000031:analogs & derivatives / Q000096:biosynthesis; D014443:Tyrosine / Q000378:metabolism
D001679:Biogenic Amines; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D006220:Haloperidol; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine; D014439:Tyramine