PMID- 22741574
OWN - NLM
STAT- MEDLINE
DCOM- 20131029
LR  - 20141120
IS  - 1369-1600 (Electronic)
IS  - 1355-6215 (Linking)
VI  - 18
IP  - 4
DP  - 2013 Jul
TI  - Substituting a long-acting dopamine uptake inhibitor for cocaine prevents relapse 
      to cocaine seeking.
PG  - 633-43
LID - 10.1111/j.1369-1600.2012.00458.x [doi]
AB  - The treatment of cocaine addiction remains a challenge. The dopamine replacement 
      approach in cocaine addiction involves the use of a competing dopaminergic 
      agonist that might suppress withdrawal and drug craving in abstinent individuals. 
      Although it has long been postulated that such an approach may be therapeutically 
      successful, preclinical or clinical evidence showing its effectiveness to prevent 
      relapse is scant. We used in rats a procedure that involved substitution of the 
      N-substituted benztropine analog 3alpha-[bis(4'-fluorophenyl)methoxy]-tropane 
      (AHN-1055), a long-acting dopamine uptake inhibitor (DUI), for cocaine. 
      Maintenance treatment was self-administered. After extinction, reinstatement of 
      drug seeking was induced by cocaine priming. We measured the contents of 
      brain-derived neurotrophic factor (BDNF), c-Fos and Fas-associated death domain 
      (FADD) proteins in the medial prefrontal cortex (mPFC) following reinstatement. 
      DUI, but not amphetamine, substitution led to extinction of active lever presses, 
      as did saline substitution. DUI substitution significantly reduced 
      cocaine-induced reinstatement of drug-seeking behavior, which was strongly 
      elicited after saline substitution. Rats passively yoked to DUI also showed 
      reduced cocaine-primed reinstatement. Reductions in drug seeking during 
      reinstatement were matched by downward shifts in the contents of BDNF, c-Fos and 
      FADD proteins in the mPFC, which were elevated in relapsing rats. These data 
      indicate that DUI substitution not only leads to extinction of 
      self-administration behavior but also prevents reinstatement of drug seeking 
      induced by cocaine re-exposure. Thus, DUI substitution therapy using compounds 
      with low abuse potential, even if received passively in the context previously 
      paired with drug taking, may provide an effective treatment for stimulant 
      addiction.
CI  - (c) 2012 The Authors, Addiction Biology (c) 2012 Society for the Study of Addiction.
FAU - Velazquez-Sanchez, Clara
AU  - Velazquez-Sanchez C
AD  - Behavioural Neuroscience, Department of Psychology, University of Canterbury, New 
      Zealand.
FAU - Ferragud, Antonio
AU  - Ferragud A
FAU - Ramos-Miguel, Alfredo
AU  - Ramos-Miguel A
FAU - Garcia-Sevilla, Jesus A
AU  - Garcia-Sevilla JA
FAU - Canales, Juan J
AU  - Canales JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120628
PL  - United States
TA  - Addict Biol
JT  - Addiction biology
JID - 9604935
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (N-methyl-3-(bis(4'-fluorophenyl)methoxy)tropane)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 1NHL2J4X8K (Benztropine)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Addictive/drug therapy/metabolism
MH  - Benztropine/administration & dosage/*analogs & 
      derivatives/pharmacology/therapeutic use
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cocaine/*administration & dosage/pharmacology
MH  - Cocaine-Related Disorders/*drug therapy/metabolism
MH  - Dopamine Uptake Inhibitors/administration & dosage/pharmacology/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug-Seeking Behavior/*drug effects
MH  - Extinction, Psychological/drug effects
MH  - Fas-Associated Death Domain Protein/metabolism
MH  - Humans
MH  - Male
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Rats
MH  - Rats, Long-Evans
MH  - Reinforcement Schedule
MH  - Secondary Prevention
MH  - Self Administration
MH  - Substance Withdrawal Syndrome/drug therapy
EDAT- 2012/06/30 06:00
MHDA- 2013/10/30 06:00
CRDT- 2012/06/30 06:00
PHST- 2012/06/30 06:00 [entrez]
PHST- 2012/06/30 06:00 [pubmed]
PHST- 2013/10/30 06:00 [medline]
AID - 10.1111/j.1369-1600.2012.00458.x [doi]
PST - ppublish
SO  - Addict Biol. 2013 Jul;18(4):633-43. doi: 10.1111/j.1369-1600.2012.00458.x. Epub 
      2012 Jun 28.