PMID- 18082673
OWN - NLM
STAT- MEDLINE
DCOM- 20080506
LR  - 20220331
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1190
DP  - 2008 Jan 23
TI  - Tyrosine depletion lowers dopamine synthesis and desipramine-induced prefrontal 
      cortex catecholamine levels.
PG  - 39-48
AB  - The relationship between limited tyrosine availability, DA (dopamine) synthesis 
      and DA levels in the medial prefrontal cortex (MPFC) of the rat was examined by 
      in vivo microdialysis. We administered a tyrosine- and phenylalanine-free mixture 
      of large neutral amino acids (LNAA-) IP to lower brain tyrosine, and the 
      norepinephrine transporter inhibitor desipramine (DMI) 10 mg/kg IP to raise MPFC 
      DA levels without affecting DA synthesis. For examination of DOPA levels, 
      NSD-1015 20 microM was included in perfusate. Neither NSD-1015 nor DMI affected 
      tyrosine levels. LNAA- lowered tyrosine levels by 45%, and lowered DOPA levels as 
      well; this was not additionally affected by concurrent DMI 10 mg/kg IP. In 
      parallel studies DMI markedly increased extracellular levels of DA (420% 
      baseline) and norepinephrine (NE) (864% baseline). LNAA- had no effect on 
      baseline levels of DA or NE but robustly lowered DMI-induced DA (176% baseline) 
      as well as NE (237% baseline) levels. Even when DMI (20 microM) was administered 
      in perfusate, LNAA- still lowered DMI-induced DA and NE levels. We conclude that 
      while baseline mesocortical DA synthesis is indeed dependent on tyrosine 
      availability, the MPFC maintains normal extracellular DA and NA levels in the 
      face of moderately lower DA synthesis. During other than baseline conditions, 
      however, tyrosine depletion can lower ECF DA and NE levels in MPFC. These data 
      offer a potential mechanism linking dysregulation of tyrosine transport and 
      cognitive deficits in schizophrenia.
FAU - Bongiovanni, Rodolfo
AU  - Bongiovanni R
AD  - Psychiatry Service, Louis Stokes Cleveland Veterans Affairs Medical Center, 
      Brecksville, OH 44141, USA.
FAU - Newbould, Erica
AU  - Newbould E
FAU - Jaskiw, George E
AU  - Jaskiw GE
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20071104
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Norepinephrine Plasma Membrane Transport Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - 63-84-3 (Dihydroxyphenylalanine)
RN  - TG537D343B (Desipramine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Animals
MH  - Desipramine/pharmacology
MH  - Dihydroxyphenylalanine/*metabolism
MH  - Dopamine/*metabolism
MH  - Male
MH  - Microdialysis
MH  - Norepinephrine/*metabolism
MH  - Norepinephrine Plasma Membrane Transport Proteins/drug effects/metabolism
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tyrosine/deficiency/*metabolism
EDAT- 2007/12/18 09:00
MHDA- 2008/05/07 09:00
CRDT- 2007/12/18 09:00
PHST- 2007/09/12 00:00 [received]
PHST- 2007/10/20 00:00 [revised]
PHST- 2007/10/28 00:00 [accepted]
PHST- 2007/12/18 09:00 [pubmed]
PHST- 2008/05/07 09:00 [medline]
PHST- 2007/12/18 09:00 [entrez]
AID - S0006-8993(07)02612-1 [pii]
AID - 10.1016/j.brainres.2007.10.079 [doi]
PST - ppublish
SO  - Brain Res. 2008 Jan 23;1190:39-48. doi: 10.1016/j.brainres.2007.10.079. Epub 2007 
      Nov 4.