TY - JOUR
T1 - An Inducer for Glial Cell Line-Derived Neurotrophic Factor and Tumor Necrosis Factor-α Protects Against Methamphetamine-Induced Rewarding Effects and Sensitization
AU - Niwa, Minae
AU - Nitta, Atsumi
AU - Yamada, Yuichiro
AU - Nakajima, Akira
AU - Saito, Kuniaki
AU - Seishima, Mitsuru
AU - Shen, Liya
AU - Noda, Yukihiro
AU - Furukawa, Shoei
AU - Nabeshima, Toshitaka
N1 - Funding Information:
This study was supported in part by a Grant-in-aid for Scientific Research and Special Coordination Funds for Promoting Science and Technology, Target-Oriented Brain Science Research Program; by a Grant-in-aid for Scientific Research (B) and Young Scientists (A); by the 21st Century Center of Excellence Program “Integrated Molecular Medicine for Neuronal and Neoplastic Disorders” from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by a Grant-in-aid for Health Science Research on Regulatory Science of Pharmaceuticals and Medical Devices, and Comprehensive Research on Aging and Health from the Ministry of Health, Labor and Welfare of Japan; by a Smoking Research Foundation Grant for Biomedical Research; by the Mochida Memorial Foundation for Medical and Pharmaceutical Research; by a grant from the Brain Research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea; and by Japan Canada Joint Health Research Program.
PY - 2007/4/1
Y1 - 2007/4/1
N2 - Background: There are few efficacious medications for drug dependence. We investigated the potential of Leu-Ile, which induces the expression of glial cell line-derived neurotrophic factor (GDNF) and tumor necrosis factor-α (TNF-α), as a novel therapeutic agent for methamphetamine (METH)-induced dependence. Methods: The levels of GDNF and TNF-α messenger RNA (mRNA) were determined by real-time reverse transcription polymerase chain reaction. Enzyme immunoassays and immunohistochemistry were employed to determine levels of these proteins. Effects of Leu-Ile on METH-induced rewarding effects and sensitization were investigated with conditioned place preference and locomotor activity tests. Extracellular dopamine (DA) levels and DA uptake into synaptosomes were examined with an in vivo microdialysis and trititated thymidine ([3H]) DA uptake assay. Results: Leu-Ile induced the expression of not only GDNF but also TNF-α. Pretreatment with Leu-Ile blocked the acquisition of METH-induced place preference and sensitization. Interestingly, post-treatment with Leu-Ile attenuated them even after their development. An inhibitory effect of Leu-Ile on METH-induced place preference was observed in neither GDNF heterozygous nor TNF-α knockout mice. Leu-Ile inhibited DA release in the nucleus accumbens and the decrease in synaptosomal DA uptake in the midbrain induced by repeated METH treatment. Conclusions: These results suggest that Leu-Ile inhibits METH-induced rewarding effects and sensitization by regulating extracellular DA levels via the induction of GDNF and TNF-α expression.
AB - Background: There are few efficacious medications for drug dependence. We investigated the potential of Leu-Ile, which induces the expression of glial cell line-derived neurotrophic factor (GDNF) and tumor necrosis factor-α (TNF-α), as a novel therapeutic agent for methamphetamine (METH)-induced dependence. Methods: The levels of GDNF and TNF-α messenger RNA (mRNA) were determined by real-time reverse transcription polymerase chain reaction. Enzyme immunoassays and immunohistochemistry were employed to determine levels of these proteins. Effects of Leu-Ile on METH-induced rewarding effects and sensitization were investigated with conditioned place preference and locomotor activity tests. Extracellular dopamine (DA) levels and DA uptake into synaptosomes were examined with an in vivo microdialysis and trititated thymidine ([3H]) DA uptake assay. Results: Leu-Ile induced the expression of not only GDNF but also TNF-α. Pretreatment with Leu-Ile blocked the acquisition of METH-induced place preference and sensitization. Interestingly, post-treatment with Leu-Ile attenuated them even after their development. An inhibitory effect of Leu-Ile on METH-induced place preference was observed in neither GDNF heterozygous nor TNF-α knockout mice. Leu-Ile inhibited DA release in the nucleus accumbens and the decrease in synaptosomal DA uptake in the midbrain induced by repeated METH treatment. Conclusions: These results suggest that Leu-Ile inhibits METH-induced rewarding effects and sensitization by regulating extracellular DA levels via the induction of GDNF and TNF-α expression.
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U2 - 10.1016/j.biopsych.2006.06.016
DO - 10.1016/j.biopsych.2006.06.016
M3 - Article
C2 - 17046726
AN - SCOPUS:33947128634
SN - 0006-3223
VL - 61
SP - 890
EP - 901
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 7
ER -