PMID- 23164454
OWN - NLM
STAT- MEDLINE
DCOM- 20140103
LR  - 20211021
IS  - 1469-5111 (Electronic)
IS  - 1461-1457 (Print)
IS  - 1461-1457 (Linking)
VI  - 16
IP  - 5
DP  - 2013 Jun
TI  - Chronic valproate attenuates some, but not all, facets of mania-like behaviour in 
      mice.
PG  - 1021-31
LID - 10.1017/S1461145712001198 [doi]
AB  - Bipolar disorder (BD) mania is a psychiatric disorder with multifaceted symptoms. 
      Development of targeted treatments for BD mania may benefit from animal models 
      that mimic multiple symptoms, as opposed to hyperactivity alone. Using the 
      reverse-translated multivariate exploratory paradigm, the behavioural pattern 
      monitor (BPM), we reported that patients with BD mania exhibit hyperactivity as 
      well as increased specific exploration and more linear movements through space. 
      This abnormal profile is also observed in mice with reduced function of the 
      dopamine transporter (DAT) through either constitutive genetic [knockdown (KD)] 
      or acute pharmacological (GBR12909) means. Here, we assessed the pharmacological 
      predictive validity of these models by administering the BD-treatment valproic 
      acid (VPA) for 28 d. After 1.5% VPA- or regular-chow treatment for 28 d, C57BL/6J 
      mice received GBR12909 (9 mg/kg) or saline and were tested in the BPM. Similarly, 
      DAT KD and wild type (WT) littermates were treated with VPA-chow and tested in 
      the BPM. GBR12909-treated and DAT KD mice on regular chow were hyperactive, 
      exhibited increased specific exploration and moved in straighter patterns 
      compared to saline-treated and WT mice respectively. Chronic 1.5% VPA-chow 
      treatment resulted in therapeutic concentrations of VPA and ameliorated 
      hyperactivity in both models, while specific exploration and behavioural 
      organization remained unaffected. Hence, the mania-like profile of mice with 
      reduced functional DAT was partially attenuated by chronic VPA treatment, 
      consistent with the incomplete symptomatic effect of VPA treatment in BD 
      patients. Both DAT models may help to identify therapeutics that impact the full 
      spectrum of BD mania.
FAU - van Enkhuizen, Jordy
AU  - van Enkhuizen J
AD  - Department of Psychiatry, University of California San Diego, CA 92093-0804, USA.
FAU - Geyer, Mark A
AU  - Geyer MA
FAU - Kooistra, Klaas
AU  - Kooistra K
FAU - Young, Jared W
AU  - Young JW
LA  - eng
GR  - R01 MH071916/MH/NIMH NIH HHS/United States
GR  - R21 MH091571/MH/NIMH NIH HHS/United States
GR  - R21-MH091571/MH/NIMH NIH HHS/United States
GR  - R01-MH071916/MH/NIMH 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 - 20121120
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 0 (Antimanic Agents)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Piperazines)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - 90X28IKH43 (vanoxerine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Antimanic Agents/*therapeutic use
MH  - Bipolar Disorder/blood/*drug therapy/genetics
MH  - Disease Models, Animal
MH  - Dopamine Plasma Membrane Transport Proteins/deficiency
MH  - Dopamine Uptake Inhibitors/therapeutic use
MH  - Exploratory Behavior/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Motor Activity/drug effects
MH  - Piperazines/therapeutic use
MH  - Time Factors
MH  - Valproic Acid/blood/*therapeutic use
PMC - PMC3920978
MID - NIHMS551413
COIS- Statement of Interest Mr. van Enkhuizen and Kooistra report no conflict of 
      interest. Dr. Geyer has received consulting compensation from Abbott, Cerca, 
      Merck, Omeros, Takeda, and Teva, and holds an equity interest in San Diego 
      Instruments. Dr. Geyer also has research grant support from Intracellular 
      Therapeutics, Johnson & Johnson, NIDA, NIMH, and the U.S. Veteran's 
      Administration VISN 22 Mental Illness Research, Education, and Clinical Center. 
      Dr. Young has received research grant support from Cerca Insights and Lundbeck 
      Ltd. The aforementioned support did not direct any of the research presented 
      here.
EDAT- 2012/11/21 06:00
MHDA- 2014/01/05 06:00
PMCR- 2014/02/11
CRDT- 2012/11/21 06:00
PHST- 2012/11/21 06:00 [entrez]
PHST- 2012/11/21 06:00 [pubmed]
PHST- 2014/01/05 06:00 [medline]
PHST- 2014/02/11 00:00 [pmc-release]
AID - S1461145712001198 [pii]
AID - 10.1017/S1461145712001198 [doi]
PST - ppublish
SO  - Int J Neuropsychopharmacol. 2013 Jun;16(5):1021-31. doi: 
      10.1017/S1461145712001198. Epub 2012 Nov 20.