PMID- 20167208
OWN - NLM
STAT- MEDLINE
DCOM- 20100719
LR  - 20220321
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1325
DP  - 2010 Apr 14
TI  - Motivational effects on interval timing in dopamine transporter (DAT) knockdown 
      mice.
PG  - 89-99
LID - 10.1016/j.brainres.2010.02.034 [doi]
AB  - We examined interval timing in mice that underexpress the dopamine transporter 
      (DAT) and have chronically higher levels of extracellular dopamine (Zhuang et 
      al., 2001). The dopaminergic system has been proposed as a neural substrate for 
      an internal clock, with transient elevations of dopaminergic activity producing 
      underestimation of temporal intervals. A group of DAT knockdown (KD) and 
      littermate wild type (WT) mice were tested with a dual peak procedure. Mice 
      obtained reinforcement by pressing one of two levers after a fixed amount of time 
      (30 or 45 s) had elapsed since lever extension. Only one lever was available at a 
      time, and each lever was associated with a single duration. On occasional probe 
      trials, the DAT KD mice began responding earlier in the interval than WT mice, 
      but showed maximal responding and terminated responding around the same time as 
      the WT mice. Administration of raclopride (0.2, 0.6, and 1.2 mg/kg), a D2 
      antagonist, eliminated most of the differences between DAT KD and WT mice, 
      suggesting that the effects of chronic DAT downregulation on interval timing were 
      mediated by the D2 receptors. Another cohort of DAT KD mice was trained on a 
      visual attention task, and no deficits were observed, confirming that the changes 
      in timed behavior were not attentionally mediated. Our data are consistent with 
      the view that tonic dopamine affects the sensitivity of an organism to external 
      reward signals, and that this increased motivation for reward of DAT KD mice 
      lowers the threshold for initiating responding in a timing task.
CI  - Copyright 2010 Elsevier B.V. All rights reserved.
FAU - Balci, Fuat
AU  - Balci F
AD  - PsychoGenics Inc, Tarrytown, NY, USA. fbalci@princeton.edu
FAU - Ludvig, Elliot A
AU  - Ludvig EA
FAU - Abner, Ron
AU  - Abner R
FAU - Zhuang, Xiaoxi
AU  - Zhuang X
FAU - Poon, Patrick
AU  - Poon P
FAU - Brunner, Dani
AU  - Brunner D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100216
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Dopamine D2 Receptor Antagonists)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Receptors, Dopamine D2)
RN  - 430K3SOZ7G (Raclopride)
SB  - IM
MH  - Animals
MH  - Attention/physiology
MH  - Dopamine Antagonists/administration & dosage/pharmacology
MH  - Dopamine D2 Receptor Antagonists
MH  - Dopamine Plasma Membrane Transport Proteins/deficiency/genetics/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Gene Knockdown Techniques
MH  - Male
MH  - Mice
MH  - Motivation/drug effects/*physiology
MH  - Neuropsychological Tests
MH  - Psychomotor Performance/drug effects/physiology
MH  - Raclopride/administration & dosage/pharmacology
MH  - Reaction Time
MH  - Receptors, Dopamine D2/metabolism
MH  - Reinforcement, Psychology
MH  - Time Factors
MH  - Time Perception/drug effects/*physiology
MH  - Visual Perception/physiology
EDAT- 2010/02/20 06:00
MHDA- 2010/07/20 06:00
CRDT- 2010/02/20 06:00
PHST- 2009/10/24 00:00 [received]
PHST- 2010/02/08 00:00 [revised]
PHST- 2010/02/09 00:00 [accepted]
PHST- 2010/02/20 06:00 [entrez]
PHST- 2010/02/20 06:00 [pubmed]
PHST- 2010/07/20 06:00 [medline]
AID - S0006-8993(10)00381-1 [pii]
AID - 10.1016/j.brainres.2010.02.034 [doi]
PST - ppublish
SO  - Brain Res. 2010 Apr 14;1325:89-99. doi: 10.1016/j.brainres.2010.02.034. Epub 2010 
      Feb 16.