TY - JOUR
T1 - Involvement of glial cell line-derived neurotrophic factor in inhibitory effects of a hydrophobic dipeptide Leu-Ile on morphine-induced sensitization and rewarding effects
AU - Niwa, Minae
AU - Nitta, Atsumi
AU - Shen, Liya
AU - Noda, Yukihiro
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 Dementia and Fracture from the Ministry of Health, Labor and Welfare of Japan; by the Japan Society for the Promotion of Science Joint Research Project under the Japan-Korea Basic Scientific Cooperation Program; 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 the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea; and by the Japan Canada Joint Health Research Program.
PY - 2007/4/16
Y1 - 2007/4/16
N2 - There are few efficacious medications for drug dependence at present. We have previously demonstrated that Leu-Ile, which induces the expression of not only tumor necrosis factor-α (TNF-α) but also glial cell line-derived neurotrophic factor (GDNF), inhibits methamphetamine (METH) and morphine (MOR)-induced sensitization and rewarding effects by regulating extracellular dopamine levels via the induction of TNF-α expression, and indicated the potential of Leu-Ile as a novel therapeutic agent for METH and MOR-induced dependence. In the present study, we investigated the involvement of GDNF in inhibitory effects of Leu-Ile on MOR-induced sensitization and rewarding effects. Repeated treatment with MOR for 9 days, which results in an enhancement of the locomotor-stimulating effects (sensitization) of MOR, increased GDNF levels in the nucleus accumbens compared with those in saline-treated mice. Repeated pre-treatment with Leu-Ile for 9 days potentiated the MOR-induced increase in GDNF levels. MOR at a low dose (3 mg/kg) produced place preference in GDNF heterozygous knockout (GDNF-(+/-)) mice, but not in littermate GDNF-(+/+) mice. No inhibitory effect of Leu-Ile on MOR-induced place preference was observed in GDNF-(+/-) mice. These results suggest that GDNF is involved in the inhibitory effects of Leu-Ile on MOR-induced sensitization and rewarding effects.
AB - There are few efficacious medications for drug dependence at present. We have previously demonstrated that Leu-Ile, which induces the expression of not only tumor necrosis factor-α (TNF-α) but also glial cell line-derived neurotrophic factor (GDNF), inhibits methamphetamine (METH) and morphine (MOR)-induced sensitization and rewarding effects by regulating extracellular dopamine levels via the induction of TNF-α expression, and indicated the potential of Leu-Ile as a novel therapeutic agent for METH and MOR-induced dependence. In the present study, we investigated the involvement of GDNF in inhibitory effects of Leu-Ile on MOR-induced sensitization and rewarding effects. Repeated treatment with MOR for 9 days, which results in an enhancement of the locomotor-stimulating effects (sensitization) of MOR, increased GDNF levels in the nucleus accumbens compared with those in saline-treated mice. Repeated pre-treatment with Leu-Ile for 9 days potentiated the MOR-induced increase in GDNF levels. MOR at a low dose (3 mg/kg) produced place preference in GDNF heterozygous knockout (GDNF-(+/-)) mice, but not in littermate GDNF-(+/+) mice. No inhibitory effect of Leu-Ile on MOR-induced place preference was observed in GDNF-(+/-) mice. These results suggest that GDNF is involved in the inhibitory effects of Leu-Ile on MOR-induced sensitization and rewarding effects.
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U2 - 10.1016/j.bbr.2007.01.026
DO - 10.1016/j.bbr.2007.01.026
M3 - Article
C2 - 17331595
AN - SCOPUS:33947309584
SN - 0166-4328
VL - 179
SP - 167
EP - 171
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1
ER -