PMID- 16541248
OWN - NLM
STAT- MEDLINE
DCOM- 20060928
LR  - 20181113
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 185
IP  - 4
DP  - 2006 May
TI  - In rats chronically treated with clozapine, tyrosine depletion attenuates the 
      clozapine-induced in vivo increase in prefrontal cortex dopamine and 
      norepinephrine levels.
PG  - 416-22
AB  - We previously reported that depletion of brain tyrosine attenuated the acute 
      clozapine (CLZ)-induced increase in medial prefrontal cortex (MPFC) dopamine (DA) 
      levels. This effect was now examined after chronic CLZ treatment. Male rats 
      received CLZ (10 mg kg(-1) day(-1)) in drinking water for 21 days. On day 18, a 
      cannula was stereotaxically implanted over the MPFC. A microdialysis probe was 
      inserted on day 20. On day 21 after a stable baseline was reached, rats received 
      an acute injection of vehicle (VEH) or a tyrosine- and phenylalanine-free mixture 
      of neutral amino acid [NAA(-)] (total 1 g kg(-1), i.p., two injections, 1 h 
      apart) followed by CLZ (10 mg kg(-1), i.p.) or VEH. Basal tyrosine or 
      norepinephrine (NE) levels were not different between the groups, but basal DA 
      was higher in the group treated chronically with CLZ (p<0.05). Acute CLZ (10 mg 
      kg(-1), i.p.) increased MPFC DA and NE levels to 370% and 510% of baseline, 
      respectively, and similarly in rats chronically pretreated with CLZ or VEH. 
      NAA(-) did not affect basal MPFC DA or NE levels but significantly attenuated 
      acute CLZ-induced DA (220% of baseline) and NE (330% of baseline) levels (p<0.01) 
      in rats pretreated chronically with CLZ or with VEH. These data demonstrate that 
      even after chronic CLZ administration, the acute CLZ-induced increases in MPFC DA 
      and NE levels depend on the availability of brain tyrosine. Judicious 
      manipulation of brain tyrosine levels may provide a useful probe as well as a 
      mechanism for enhancing psychotropic drug actions.
FAU - Jaskiw, George E
AU  - Jaskiw GE
AD  - Louis Stokes Department of Veterans Affairs Medical Center, Cleveland, OH, USA. 
      gxj5@case.edu
FAU - Kirkbride, Bobbi
AU  - Kirkbride B
FAU - Bongiovanni, Rodolfo
AU  - Bongiovanni R
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 - 20060316
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Amino Acids)
RN  - 0 (Antipsychotic Agents)
RN  - 42HK56048U (Tyrosine)
RN  - J60AR2IKIC (Clozapine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Amino Acids/metabolism
MH  - Animals
MH  - Antipsychotic Agents/*pharmacology
MH  - Chromatography, High Pressure Liquid
MH  - Clozapine/*pharmacology
MH  - Dopamine/*metabolism
MH  - Male
MH  - Microdialysis
MH  - Norepinephrine/*metabolism
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tyrosine/deficiency/*physiology
EDAT- 2006/03/17 09:00
MHDA- 2006/09/29 09:00
CRDT- 2006/03/17 09:00
PHST- 2005/03/28 00:00 [received]
PHST- 2005/11/28 00:00 [accepted]
PHST- 2006/03/17 09:00 [pubmed]
PHST- 2006/09/29 09:00 [medline]
PHST- 2006/03/17 09:00 [entrez]
AID - 10.1007/s00213-005-0283-1 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2006 May;185(4):416-22. doi: 
      10.1007/s00213-005-0283-1. Epub 2006 Mar 16.