PMID- 12099907
OWN - NLM
STAT- MEDLINE
DCOM- 20020904
LR  - 20191210
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 15
IP  - 12
DP  - 2002 Jun
TI  - Role of the dopamine D3 receptor in reactivity to cocaine-associated cues in 
      mice.
PG  - 2016-26
AB  - Environmental stimuli previously associated with drug effects can acquire 
      secondary reinforcing properties, able to maintain drug-seeking behaviour or 
      induce relapse. We have used a classical Pavlovian conditioning procedure to 
      assess the role of the dopamine D3 receptor (D3R) in the expression of 
      drug-conditioned responses. Mice repeatedly receiving cocaine in a particular 
      environment distinct from home-cages displayed hyperlocomotion after subsequent 
      exposure to the drug-paired environment. Cocaine-conditioned hyperactivity was 
      inhibited by BP 897 or SB-277011-A, D3R-selective partial agonist and antagonist, 
      respectively. D3R gene-targeted mice showed a trend towards an increase in 
      cocaine cue-conditioned hyperactivity. BP 897 had no effect on reactivity to 
      neutral or aversive cues. Cocaine-conditioned mice had increased levels of D3R 
      mRNA and binding in the nucleus accumbens (NAc), and transcripts of brain-derived 
      neurotrophic factor (BDNF), a factor controlling D3R expression, in the ventral 
      tegmental area (VTA). Cocaine had no effects on D3R or BDNF genes when 
      administered in home-cages. Cocaine cue-conditioned c-fos expression was found in 
      cortical areas, notably in the somatosensory cortex, where it was inhibited by BP 
      897, and in several regions belonging or linked to the limbic system. In 
      conditioned mice, BP 897 inhibited c-fos expression in VTA and activated it in 
      amygdala. These results demonstrate a modulation of reactivity to cocaine cues by 
      the D3R, the expression of which is elevated in the NAc by the repeated 
      association of drug effects with a particular context, through a BDNF-dependent 
      mechanism. D3R-selective partial agonist or antagonist inhibit cocaine 
      cue-conditioned activity possibly by normalizing exacerbated D3R function in the 
      NAc, but our results also point to a possible participation of a pathway 
      involving the VTA, amygdala and somatosensory cortex.
FAU - Le Foll, Bernard
AU  - Le Foll B
AD  - Unite de Neurobiologie et Pharmacologie Moleculaire (INSERM U 573), Centre Paul 
      Broca, 75014 Paris, France.
FAU - Frances, Henriette
AU  - Frances H
FAU - Diaz, Jorge
AU  - Diaz J
FAU - Schwartz, Jean-Charles
AU  - Schwartz JC
FAU - Sokoloff, Pierre
AU  - Sokoloff P
LA  - eng
GR  - R01-DA11534/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Agonists)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Drd3 protein, mouse)
RN  - 0 (Piperazines)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Receptors, Dopamine D3)
RN  - 20PLE5W821 (BP 897)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/*metabolism/physiopathology
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Cocaine/*pharmacology
MH  - Cocaine-Related Disorders/*metabolism/physiopathology
MH  - Conditioning, Psychological/drug effects/*physiology
MH  - *Cues
MH  - Dopamine Agonists/pharmacology
MH  - Dopamine Antagonists/pharmacology
MH  - Dopamine Uptake Inhibitors/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression/drug effects/physiology
MH  - Genotype
MH  - Hyperkinesis/chemically induced/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Piperazines/pharmacology
MH  - Proto-Oncogene Proteins c-fos/genetics
MH  - RNA, Messenger/drug effects/metabolism
MH  - Receptors, Dopamine D2/*deficiency/drug effects/genetics
MH  - Receptors, Dopamine D3
MH  - *Reinforcement, Psychology
MH  - Up-Regulation/drug effects/physiology
EDAT- 2002/07/09 10:00
MHDA- 2002/09/06 10:01
CRDT- 2002/07/09 10:00
PHST- 2002/07/09 10:00 [pubmed]
PHST- 2002/09/06 10:01 [medline]
PHST- 2002/07/09 10:00 [entrez]
AID - 2049 [pii]
AID - 10.1046/j.1460-9568.2002.02049.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2002 Jun;15(12):2016-26. doi: 10.1046/j.1460-9568.2002.02049.x.