[Dynamics and functional analysis of cytokines/proteinases with drug dependence].
Drug addiction/dependence is defined as a chronically relapsing disorder that is characterized by compulsive drug taking, inability to limit the intake, and intense drug craving. The positive reinforcing/rewarding effects of drugs of abuse depend mainly on the mesocorticolimbic dopamine system innervating the nucleus accumbens. It is widely accepted that chronic intake of drugs of abuse causes stable changes in the structure and function of the brain, which may be associated with development of drug dependence as well as the long-lived vulnerability to relapse. Recent evidence has demonstrated that various cytokines and proteinases participate to the development and relapse of drug dependence, which may be divided into two groups. Pro-addictive factors that act to potentiate the rewarding effect of drugs include bFGF, BDNF, tPA, MMP-2 and MMP-9. Anti-addictive factors such as TNF-a and GDNF act to reduce the rewarding effect of drugs of abuse. These findings suggest that an imbalance between pro-addictive and anti-addictive factors contributes to the development and relapse of drug dependence.
Yamada
Kiyofumi
K
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan. kyamada@med.nagoya-u.ac.jp
D000818:Animals; D001921:Brain / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000502:physiology; D006801:Humans; D020782:Matrix Metalloproteinases / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D010447:Peptide Hydrolases / Q000502:physiology*; D012008:Recurrence; D019966:Substance-Related Disorders / Q000235:genetics*; D013569:Synapses / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D051100:Glial Cell Line-Derived Neurotrophic Factor; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D020782:Matrix Metalloproteinases; D004298:Dopamine