PMID- 23371490
OWN - NLM
STAT- MEDLINE
DCOM- 20131028
LR  - 20211021
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 227
IP  - 2
DP  - 2013 May
TI  - Presynaptic regulation of extracellular dopamine levels in the medial prefrontal 
      cortex and striatum during tyrosine depletion.
PG  - 363-71
LID - 10.1007/s00213-013-2977-0 [doi]
AB  - RATIONALE: Available neurochemical probes that lower brain dopamine (DA) levels 
      in man are limited by their tolerability and efficacy. For instance, the acute 
      lowering of brain tyrosine is well tolerated, but only modestly lowers brain DA 
      levels. Modification of tyrosine depletion to robustly lower DA levels would 
      provide a superior research probe. OBJECTIVES: The objective of this study was to 
      determine whether the subthreshold stimulation of presynaptic DA receptors would 
      potentiate tyrosine depletion-induced effects on extracellular DA levels in the 
      medial prefrontal cortex (MPFC) and striatum of the rat. METHODS: We administered 
      quinpirole, a predominantly DA type 2 (D2R) receptor agonist, into the MPFC and 
      striatum by reverse dialysis. A tyrosine- and phenylalanine-free neutral amino 
      acid mixture [NAA(-)] IP was used to lower brain tyrosine levels. DA levels in 
      the microdialysate were measured by HPLC with electrochemical detection. RESULTS: 
      Quinpirole dose-dependently lowered DA levels in MPFC as well as in the striatum. 
      NAA(-) alone transiently lowered DA levels (80 % baseline) in the striatum, but 
      had no effect in MPFC. The co-administration of NAA(-) and a subthreshold 
      concentration of quinpirole (6.25 nM) lowered DA levels (50 % baseline) in both 
      the MPFC and striatum. This effect was blocked by the mixed D2R/D3R antagonist 
      haloperidol at IP doses that on their own did not affect DA levels (10.0 nmol/kg 
      in the MPFC and 0.10 nmol/kg in the striatum). CONCLUSIONS: Pharmacological 
      stimulation of inhibitory D2R receptors during tyrosine depletion markedly lowers 
      the extracellular DA levels in the MPFC and striatum. The data suggest that 
      combining tyrosine depletion with a low dose of a DA agonist should robustly 
      lower brain regional DA levels in man.
FAU - Brodnik, Zachary
AU  - Brodnik Z
AD  - Louis Stokes Cleveland DVAMC, Research Service, 151W 10701 East Blvd, Cleveland, 
      OH 44106, USA.
FAU - Double, Manda
AU  - Double M
FAU - Jaskiw, George E
AU  - Jaskiw GE
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130201
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Amino Acids)
RN  - 0 (Dopamine Agonists)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Receptors, Dopamine D2)
RN  - 20OP60125T (Quinpirole)
RN  - 42HK56048U (Tyrosine)
RN  - J6292F8L3D (Haloperidol)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Amino Acids/administration & dosage
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Corpus Striatum/metabolism
MH  - Dopamine/*metabolism
MH  - Dopamine Agonists/administration & dosage/*pharmacology
MH  - Dopamine Antagonists/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Haloperidol/pharmacology
MH  - Male
MH  - Microdialysis
MH  - Prefrontal Cortex/metabolism
MH  - Quinpirole/administration & dosage/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine D2/drug effects/metabolism
MH  - Tyrosine/*deficiency
EDAT- 2013/02/02 06:00
MHDA- 2013/10/29 06:00
CRDT- 2013/02/02 06:00
PHST- 2012/08/07 00:00 [received]
PHST- 2012/12/21 00:00 [accepted]
PHST- 2013/02/02 06:00 [entrez]
PHST- 2013/02/02 06:00 [pubmed]
PHST- 2013/10/29 06:00 [medline]
AID - 10.1007/s00213-013-2977-0 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2013 May;227(2):363-71. doi: 
      10.1007/s00213-013-2977-0. Epub 2013 Feb 1.