Implication of brain-derived neurotrophic factor in the release of dopamine and dopamine-related behaviors induced by methamphetamine
Section snippets
Experimental procedures
The present study was conducted in accordance with the Guiding Principles for the Care and Use of Laboratory Animals, Hoshi University, as adopted by the Committee on Animal Research of Hoshi University, which is accredited by the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Histological analysis
Fig. 1 shows the placement of microdialysis probes in the nucleus accumbens. Guide cannulas were localized above the nucleus accumbens. Only data from the rats in which the probes were inserted accurately into the nucleus accumbens were used for the subsequent statistical analysis.
Effect of pretreatment with bdnf or trkb antibody into the nucleus accumbens on the meth-induced enhancement of da release and decreasing of dopac and hva in the nucleus accumbens
Table 1 shows basal levels of DA. Compared with the saline-pretreated group, basal levels of DA in the nucleus accumbens were not changed in rats that received intra-nucleus accumbens BDNF-antibody (2.0 μl,
Discussion
The nucleus accumbens has been shown to be the key brain region that underlies the action of psychostimulants and opioids such as METH, cocaine and morphine. Various studies provide evidence that METH and d-amphetamine significantly release DA in the nucleus accumbens (Di Chiara and Imperato, 1988; Zhang et al., 2001; for review see Seiden et al., 1993), which results in the expression of their DA-related actions, including drug dependence. It is also well recognized that rearing and sniffing
Conclusion
We demonstrated here that the microinjection of either BDNF or TrkB antibody into the nucleus accumbens significantly decreases the substantial elevation of extracellular DA levels by METH without any changes in the basal DA level, resulting in a significant decrease in METH-induced DA-related behaviors. These findings imply that BDNF/TrkB pathway may be involved in the expression of METH-induced DA release and its related pharmacological actions.
Acknowledgements
This work was supported in part by grants from the Ministry of Health, Labor and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology of Japan. We wish to thank Ms Naoko Kuzumaki and Ms Kaori Shibui for their expert technical assistance.
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