PMID- 16026479
OWN - NLM
STAT- MEDLINE
DCOM- 20050914
LR  - 20131121
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 21
IP  - 12
DP  - 2005 Jun
TI  - Silencing dopamine D3-receptors in the nucleus accumbens shell in vivo induces 
      changes in cocaine-induced hyperlocomotion.
PG  - 3415-26
AB  - The dopamine D(3) receptor (D(3)R) is an important pharmacotherapeutic target for 
      its potential role in psychiatric disorders and drug dependence. To further 
      explore its function in rats, a regulatable lentivirus, Lenti-D3, holding the rat 
      D(3)R cDNA, has been constructed as well as three nonregulatable lentiviruses, 
      Lenti-D3-siRNA1, Lenti-D3-siRNA2 and Lenti-D3-siRNA3, expressing small hairpin 
      RNAs, aimed at silencing D(3)R expression and specifically targeted against 
      different regions of the D(3)R mRNA. In vitro, Lenti-D3 expressed D(3)R and could 
      efficiently be blocked with Lenti-D3-Sils. These viruses were stereotaxically 
      injected into the shell part of the nucleus accumbens (NAcc) and effects of 
      passive cocaine delivery on locomotor activity were assessed. Manipulations of 
      D(3)R levels induced changes in the locomotor stimulant effects of cocaine as 
      compared to control treatment. Suppression of dopamine (DA) D(3)R in the NAcc by 
      means of local knockdown (with Lenti-D3-Sils) increased locomotor stimulant 
      effects, whereas its overexpression with Lenti-D3 drastically reduced them. The 
      latter effects could be reversed when animals were fed doxycycline, which 
      prevented lentiviral-mediated DA D(3)R overexpression in the NAcc. Gene 
      expression assessed by quantitative RT-PCR confirmed very efficient gene 
      knockdown in vivo in animals treated with Lenti-D3-Sils (> 93% silencing of D(3)R 
      gene). Thus D(3)R expression significantly contributes to behavioural changes 
      associated with chronic cocaine delivery.
FAU - Bahi, Amine
AU  - Bahi A
AD  - Institute of Biochemistry, University of Fribourg, Rue du Musee 5, CH-1700 
      Fribourg, Switzerland.
FAU - Boyer, Frederic
AU  - Boyer F
FAU - Bussard, Gaelle
AU  - Bussard G
FAU - Dreyer, Jean-Luc
AU  - Dreyer JL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (DRD3 protein, human)
RN  - 0 (Drd3 protein, rat)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Receptors, Dopamine D3)
RN  - 0 (dopamine D2L receptor)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Blotting, Northern/methods
MH  - Cell Line
MH  - Cocaine-Related Disorders/*physiopathology/therapy
MH  - Doxycycline/pharmacology
MH  - Gene Expression Regulation/drug effects/physiology
MH  - Gene Silencing/drug effects/*physiology
MH  - Genetic Vectors/physiology
MH  - Humans
MH  - Male
MH  - Motor Activity/*physiology
MH  - Nucleus Accumbens/drug effects/*metabolism
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - RNA, Messenger/biosynthesis
MH  - RNA, Small Interfering/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Dopamine D2/metabolism/*physiology
MH  - Receptors, Dopamine D3
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Transfection/methods
EDAT- 2005/07/20 09:00
MHDA- 2005/09/15 09:00
CRDT- 2005/07/20 09:00
PHST- 2005/07/20 09:00 [pubmed]
PHST- 2005/09/15 09:00 [medline]
PHST- 2005/07/20 09:00 [entrez]
AID - EJN4157 [pii]
AID - 10.1111/j.1460-9568.2005.04157.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2005 Jun;21(12):3415-26. doi: 10.1111/j.1460-9568.2005.04157.x.