PMID- 17556847
OWN - NLM
STAT- MEDLINE
DCOM- 20071002
LR  - 20131121
IS  - 0302-282X (Print)
IS  - 0302-282X (Linking)
VI  - 55
IP  - 1
DP  - 2007
TI  - Brain-derived neurotrophic factor and its intracellular signaling pathways in 
      cocaine addiction.
PG  - 2-13
AB  - Cocaine addiction is one of the severest health problems faced by western 
      countries, where there is an increasing prevalence of lifelong abuse. The most 
      challenging aspects in the treatment of cocaine addiction are craving and 
      relapse, especially in view of the fact that, at present, there is a lack of 
      effective pharmacological treatment for the disorder. What is required are new 
      pharmacological approaches based on our current understanding of the 
      neurobiological bases of drug addiction. Within the context of the behavioral and 
      neurochemical actions of cocaine, this paper considers the contribution of 
      brain-derived neurotrophic factor (BDNF) and its main intracellular signaling 
      mechanisms, including mitogen-activated protein kinase/extracellular 
      signal-regulated protein kinase (MAPK/ERK) and phosphatidylinositol 3-kinase 
      (PI3K), in psychostimulant addiction. Repeated cocaine administration leads to an 
      increase in BDNF levels and enhanced activity in the intracellular pathways (PI3K 
      and MAPK/ERK) in the reward-related brain areas, which applies especially several 
      days following withdrawal. It has been hypothesized that these neurochemical 
      changes contribute to the enduring synaptic plasticity that underlies sensitized 
      responses to psychostimulants and drug-conditioned memories leading to compulsive 
      drug use and frequent relapse after withdrawal. Nevertheless, increased BDNF 
      levels could also have a role as a protection factor in addiction. The inhibition 
      of the intracellular pathways, ERK and PI3K, leads to a disruption in sensitized 
      responses and conditioned memories associated with cocaine addiction and suggests 
      new, potential therapeutic strategies to explore in the dependence on 
      psychostimulants.
FAU - Corominas, M
AU  - Corominas M
AD  - Psychiatry Service, Vall d'Hebron Hospital, Psychiatry Department of the 
      Universitat Autonoma de Barcelona, Barcelona, Spain. mcoromin@vhebron.net
FAU - Roncero, C
AU  - Roncero C
FAU - Ribases, M
AU  - Ribases M
FAU - Castells, X
AU  - Castells X
FAU - Casas, M
AU  - Casas M
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20070608
PL  - Switzerland
TA  - Neuropsychobiology
JT  - Neuropsychobiology
JID - 7512895
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cocaine/administration & dosage
MH  - Cocaine-Related Disorders/*metabolism
MH  - Dopamine Uptake Inhibitors/administration & dosage
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Models, Biological
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Signal Transduction/drug effects/*physiology
RF  - 106
EDAT- 2007/06/09 09:00
MHDA- 2007/10/03 09:00
CRDT- 2007/06/09 09:00
PHST- 2006/05/29 00:00 [received]
PHST- 2006/12/17 00:00 [accepted]
PHST- 2007/06/09 09:00 [pubmed]
PHST- 2007/10/03 09:00 [medline]
PHST- 2007/06/09 09:00 [entrez]
AID - 000103570 [pii]
AID - 10.1159/000103570 [doi]
PST - ppublish
SO  - Neuropsychobiology. 2007;55(1):2-13. doi: 10.1159/000103570. Epub 2007 Jun 8.