PMID- 24287168
OWN - NLM
STAT- MEDLINE
DCOM- 20140917
LR  - 20211021
IS  - 1573-2517 (Electronic)
IS  - 0165-0327 (Print)
IS  - 0165-0327 (Linking)
VI  - 155
DP  - 2014 Feb
TI  - Dopamine depletion attenuates some behavioral abnormalities in a 
      hyperdopaminergic mouse model of bipolar disorder.
PG  - 247-54
LID - S0165-0327(13)00803-3 [pii]
LID - 10.1016/j.jad.2013.08.041 [doi]
AB  - BACKGROUND: Patients with BD suffer from multifaceted symptoms, including 
      hyperactive and psychomotor agitated behaviors. Previously, we quantified 
      hyperactivity, increased exploration, and straighter movements of patients with 
      BD mania in the human Behavioral Pattern Monitor (BPM). A similar BPM profile is 
      observed in mice that are hyperdopaminergic due to reduced dopamine transporter 
      (DAT) functioning. We hypothesized that dopamine depletion through 
      alpha-methyl-p-tyrosine (AMPT) administration would attenuate this mania-like 
      profile. METHODS: Male and female DAT wild-type (WT; n=26) and knockdown (KD; 
      n=28) mice on a C57BL/6 background were repeatedly tested in the BPM to assess 
      profile robustness and stability. The optimal AMPT dose was identified by 
      treating male C57BL/6 mice (n=39) with vehicle or AMPT (10, 30, or 100mg/kg) at 
      24, 20, and 4h prior to testing in the BPM. Then, male and female DAT WT (n=40) 
      and KD (n=37) mice were tested in the BPM after vehicle or AMPT (30mg/kg) 
      treatment. RESULTS: Compared to WT littermates, KD mice exhibited increased 
      activity, exploration, straighter movement, and disorganized behavior. 
      AMPT-treatment reduced hyperactivity and increased path organization, but 
      potentiated specific exploration in KD mice without affecting WT mice. 
      LIMITATIONS: AMPT is not specific to dopamine and also depletes norepinephrine. 
      CONCLUSIONS: KD mice exhibit abnormal exploration in the BPM similar to patients 
      with BD mania. AMPT-induced dopamine depletion attenuated some, but potentiated 
      other, aspects of this mania-like profile in mice. Future studies should extend 
      these findings into other aspects of mania to determine the suitability of AMPT 
      as a treatment for BD mania.
CI  - (c) 2013 Published by Elsevier B.V.
FAU - van Enkhuizen, Jordy
AU  - van Enkhuizen J
AD  - Department of Psychiatry, University of California San Diego, 9500 Gilman Drive 
      MC 0804, La Jolla, CA 92093-0804, United States; Division of Pharmacology, 
      Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 
      Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
FAU - Geyer, Mark A
AU  - Geyer MA
AD  - Department of Psychiatry, University of California San Diego, 9500 Gilman Drive 
      MC 0804, La Jolla, CA 92093-0804, United States; Research Service, VA San Diego 
      Healthcare System, San Diego, CA, United States.
FAU - Halberstadt, Adam L
AU  - Halberstadt AL
AD  - Department of Psychiatry, University of California San Diego, 9500 Gilman Drive 
      MC 0804, La Jolla, CA 92093-0804, United States.
FAU - Zhuang, Xiaoxi
AU  - Zhuang X
AD  - Department of Neurobiology, University of Chicago, Chicago, IL, United States.
FAU - Young, Jared W
AU  - Young JW
AD  - Department of Psychiatry, University of California San Diego, 9500 Gilman Drive 
      MC 0804, La Jolla, CA 92093-0804, United States; Research Service, VA San Diego 
      Healthcare System, San Diego, CA, United States. Electronic address: 
      jaredyoung@ucsd.edu.
LA  - eng
GR  - R01 DA002925/DA/NIDA NIH HHS/United States
GR  - R01 MH071916/MH/NIMH NIH HHS/United States
GR  - R01-MH071916/MH/NIMH NIH HHS/United States
GR  - R01-DA002925/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20131116
PL  - Netherlands
TA  - J Affect Disord
JT  - Journal of affective disorders
JID - 7906073
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 658-48-0 (alpha-Methyltyrosine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Bipolar Disorder/*physiopathology
MH  - *Disease Models, Animal
MH  - Dopamine/*metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/physiology
MH  - Exploratory Behavior/*physiology
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - alpha-Methyltyrosine/administration & dosage
PMC - PMC3924859
MID - NIHMS544837
OTO - NOTNLM
OT  - AMPT
OT  - Bipolar disorder
OT  - Dopamine transporter
OT  - Mania
OT  - Mice
EDAT- 2013/11/30 06:00
MHDA- 2014/09/18 06:00
PMCR- 2015/02/01
CRDT- 2013/11/30 06:00
PHST- 2013/06/26 00:00 [received]
PHST- 2013/08/12 00:00 [accepted]
PHST- 2013/11/30 06:00 [entrez]
PHST- 2013/11/30 06:00 [pubmed]
PHST- 2014/09/18 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - S0165-0327(13)00803-3 [pii]
AID - 10.1016/j.jad.2013.08.041 [doi]
PST - ppublish
SO  - J Affect Disord. 2014 Feb;155:247-54. doi: 10.1016/j.jad.2013.08.041. Epub 2013 
      Nov 16.