Original Paper

Brain-Derived Neurotrophic Factor and Its Intracellular Signaling Pathways in Cocaine Addiction
M. Corominas, C. Roncero, M. Ribases, X. Castells, M. Casas

Psychiatry Service, Vall d'Hebron Hospital, Psychiatry Department of the Universitat Autònoma de Barcelona, Barcelona, Spain

Address of Corresponding Author

Neuropsychobiology 2007;55:2-13 (DOI: 10.1159/000103570)

  Key Words

• Cocaine addiction
• Psychostimulant
• Brain-derived neurotrophic factor
• Extracellular signal-regulated protein kinase
• Phosphatidylinositol 3-kinase
• Sensitization
• Conditioning
• Craving
• Relapse

  Abstract

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.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Dr. Margarita Corominas
Psychiatry Service, Vall d'Hebron Hospital
Escola d'Enfermeria building, 5th floor, Pg. Vall d'Hebron, 119-129
ES-08035 Barcelona (Spain)
Tel. +34 93 489 42 94, Fax +34 93 489 45 87, E-Mail mcoromin@vhebron.net

  Article Information

Received: May 29, 2006
Accepted after revision: December 17, 2006
Published online: June 8, 2007
Number of Print Pages : 12
Number of Figures : 2, Number of Tables : 0, Number of References : 106