PMID- 12586455
OWN - NLM
STAT- MEDLINE
DCOM- 20030507
LR  - 20190815
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 53
IP  - 4
DP  - 2003 Feb 15
TI  - Valproate attenuates hyperactive and perseverative behaviors in mutant mice with 
      a dysregulated dopamine system.
PG  - 352-9
AB  - BACKGROUND: Dopamine transporter (DAT) knockdown (KD) mice, with approximately 
      90% loss of expression of the DAT, allow for the examination of the behavioral 
      consequences of a chronically dysregulated dopamine system. The DAT KD mice have 
      hyperdopaminergic tone, are hyperactive, and show impaired response inhibition in 
      a number of paradigms. We hypothesized that the DAT KD mice would also display 
      deficits in prepulse inhibition (PPI) and would be perseverative in their 
      locomotor behavior. METHODS: Basal levels of PPI and patterns of locomotor 
      behavior were measured in two cohorts of DAT KD mice. In addition, measurements 
      of locomotor behavior were recorded after pretreatment with 100 mg/kg valproate 
      in both DAT KD and wildtype mice. RESULTS: The DAT KD mice were hyperactive and 
      displayed perseverative motor behavior but had normal levels of PPI. The 
      clinically effective antimania drug valproate significantly attenuated the 
      hyperactivity and perseverative locomotor behavior in the DAT KD mice and had no 
      effect in control mice. CONCLUSIONS: The DAT KD mice appear to provide a model of 
      some aspects of manic behavior. With limited models of bipolar disorder, the DAT 
      KD mice might provide a vehicle to screen for new psychiatric therapies to treat 
      mania and its related symptoms.
FAU - Ralph-Williams, Rebecca J
AU  - Ralph-Williams RJ
AD  - Alcohol and Drug Abuse Research Center, Harvard Medical School and McLean 
      Hospital, Belmont, Massachusetts, USA.
FAU - Paulus, Martin P
AU  - Paulus MP
FAU - Zhuang, Xiaoxi
AU  - Zhuang X
FAU - Hen, Rene
AU  - Hen R
FAU - Geyer, Mark A
AU  - Geyer MA
LA  - eng
GR  - DA02925/DA/NIDA NIH HHS/United States
GR  - F31-MH12806/MH/NIMH NIH HHS/United States
GR  - MH42228/MH/NIMH NIH HHS/United States
GR  - MH61326/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Antimanic Agents)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Slc6a3 protein, mouse)
RN  - 0 (Slc6a3 protein, rat)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Antimanic Agents/*pharmacology
MH  - Behavior, Animal/*drug effects
MH  - Dopamine/*genetics/*physiology
MH  - Dopamine Plasma Membrane Transport Proteins
MH  - Dose-Response Relationship, Drug
MH  - Hyperkinesis/*drug therapy/genetics/*psychology
MH  - Male
MH  - *Membrane Glycoproteins
MH  - Membrane Transport Proteins/genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Motor Activity/drug effects
MH  - Mutation/physiology
MH  - *Nerve Tissue Proteins
MH  - Phenotype
MH  - Rats
MH  - Reflex, Startle/*drug effects/*genetics
MH  - Valproic Acid/*pharmacology
EDAT- 2003/02/15 04:00
MHDA- 2003/05/08 05:00
CRDT- 2003/02/15 04:00
PHST- 2003/02/15 04:00 [pubmed]
PHST- 2003/05/08 05:00 [medline]
PHST- 2003/02/15 04:00 [entrez]
AID - S0006322302014890 [pii]
AID - 10.1016/s0006-3223(02)01489-0 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2003 Feb 15;53(4):352-9. doi: 10.1016/s0006-3223(02)01489-0.