Effect of precursor loading on the synthesis rate and release of dopamine and serotonin in the striatum: a microdialysis study in conscious rats.
The effects of systemic administration of tyrosine and phenylalanine on the extracellular levels of tyrosine and dopamine were determined by microdialysis in the striatum of awake rats. In addition, the effects of these precursors on in vivo 3,4-dihydroxyphenylalanine (DOPA) formation were determined during continuous infusion of a decarboxylase inhibitor. Both precursors increased the dialysate levels of tyrosine sixfold, but only phenylalanine administration stimulated DOPA formation. However, neither precursor affected the release of dopamine. When the precursor administration was repeated in rats in which the release of dopamine was stimulated by haloperidol pretreatment, again no effect was seen on the release of dopamine. Systemic administration of tryptophan (100 mg/kg, i.p.) during continuous infusion of a decarboxylase inhibitor induced a threefold increase in the formation of 5-hydroxytryptophan and caused an increase in the release of serotonin during infusion of an uptake inhibitor to about 150% of controls. Finally, we investigated whether dietary precursors were able to influence neurotransmitter formation and release. Rats trained to consume their daily food in a period of 2 h were implanted with microdialysis probes. Scheduled eating induced a small increase in the extracellular levels of tyrosine (135% of controls), but the release of dopamine and the formation of 5-hydroxytryptophan during continuous infusion of a decarboxylase inhibitor were not affected.
Westerink
B H
BH
Department of Medicinal Chemistry, University Centre for Pharmacy, Groningen, The Netherlands.
De Vries
J B
JB
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010649:Phenylalanine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism / Q000494:pharmacology*
D012701:Serotonin; D014443:Tyrosine; D010649:Phenylalanine; D004295:Dihydroxyphenylalanine; D014364:Tryptophan; D006220:Haloperidol; D004298:Dopamine