PMID- 16934236 OWN - NLM STAT- MEDLINE DCOM- 20061204 LR - 20131121 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 1115 IP - 1 DP - 2006 Oct 18 TI - Increased striatal dopamine synthesis is associated with decreased tissue levels of tyrosine. PG - 26-36 AB - Tyrosine levels do not generally affect indices of dopamine (DA) synthesis or efflux under basal conditions, but can do so when DA synthesis is increased. One possibility is that a high rate of DA synthesis depletes the normally adequate pool of endogenous tyrosine. To study this, we administered drugs known to preferentially increase striatal DA synthesis and examined DOPA levels in striatal microdialysate during perfusion with NSD-1015. In additional groups, we also measured DA, tyrosine and large neutral amino acids in striatal microdialysate, as well as in tissue from striatum and medial prefrontal cortex (MPFC). gamma-butyrolactone (GBL) (750 mg/kg i.p.) increased DOPA levels in striatal microdialysate, increased tissue DA levels in the MPFC and striatum, but lowered tissue tyrosine levels only in striatum. In striatal microdialysate, GBL markedly lowered DA levels; tyrosine levels were only marginally lower. Haloperidol (HAL) (1.0 mg/kg s.c.)+/-amfonelic acid (AFA) (5 mg/kg i.p.) increased striatal DOPA accumulation, increased striatal DA efflux, lowered striatal tissue tyrosine levels, but did not affect microdialysate tyrosine levels. There were no consistent changes in levels of other large neutral amino acids. We conclude that increased tyrosine hydroxylation can significantly deplete the endogenous pool of tyrosine. Under such conditions, near normal extracellular tyrosine levels are maintained despite lower tissue levels. The data are consistent with a net transfer of tyrosine from non-DAergic cells to DA terminals in support of DA synthesis. FAU - Bongiovanni, Rodolfo AU - Bongiovanni R AD - Psychiatry Service, Louis Stokes Department of Veterans Affairs Medical Center, Cleveland, OH 44141, USA. FAU - Young, Damon AU - Young D FAU - Newbould, Erica AU - Newbould E FAU - Jaskiw, George E AU - Jaskiw GE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20060824 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Amino Acids) RN - 0 (Dopamine Antagonists) RN - 0 (Solvents) RN - 42HK56048U (Tyrosine) RN - 63-84-3 (Dihydroxyphenylalanine) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - J6292F8L3D (Haloperidol) RN - OL659KIY4X (4-Butyrolactone) RN - VTD58H1Z2X (Dopamine) SB - IM MH - 4-Butyrolactone/pharmacology MH - Amino Acids/analysis/metabolism MH - Animals MH - Corpus Striatum/drug effects/*metabolism MH - Dihydroxyphenylalanine/analysis/metabolism MH - Dopamine/*biosynthesis MH - Dopamine Antagonists/pharmacology MH - Down-Regulation/drug effects/physiology MH - Extracellular Fluid/drug effects/metabolism MH - Haloperidol/pharmacology MH - Hydroxylation/drug effects MH - Male MH - Microdialysis MH - Neurons/drug effects/metabolism MH - Prefrontal Cortex/drug effects/metabolism MH - Presynaptic Terminals/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Solvents MH - Tyrosine/*metabolism MH - Tyrosine 3-Monooxygenase/*metabolism MH - Up-Regulation/drug effects/physiology EDAT- 2006/08/29 09:00 MHDA- 2006/12/09 09:00 CRDT- 2006/08/29 09:00 PHST- 2006/04/11 00:00 [received] PHST- 2006/07/20 00:00 [revised] PHST- 2006/07/24 00:00 [accepted] PHST- 2006/08/29 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/08/29 09:00 [entrez] AID - S0006-8993(06)02217-7 [pii] AID - 10.1016/j.brainres.2006.07.074 [doi] PST - ppublish SO - Brain Res. 2006 Oct 18;1115(1):26-36. doi: 10.1016/j.brainres.2006.07.074. Epub 2006 Aug 24.