Gene expression profiling of rewarding effect in methamphetamine treated Bax-deficient mouse.
Methamphetamine is an illicit drug that is often abused and can cause neuropsychiatric and neurotoxic damage. Repeated administration of psychostimulants such as methamphetamine induces a behavioral sensitization. According to a previous study, Bax was involved in neurotoxicity by methamphetamine, but the function of Bax in rewarding effect has not yet been elucidated. Therefore, we have studied the function of Bax in a rewarding effect model. In the present study, we treated chronic methamphetamine exposure in a Bax-deficient mouse model and examined behavioral change using a conditioned place preference (CPP) test. The CPP score in Bax knockout mice was decreased compared to that of wild-type mice. Therefore, we screened for Bax-related genes that are involved in rewarding effect using microarray technology. In order to confirm microarray data, we applied the RT-PCR method to observe relative changes of Bcl2, a pro-apoptotic family gene. As a result, using our experiment microarray, we selected genes that were associated with Bax in microarray data, and eventually selected the Tgfbr2 gene. Expression of the Tgfbr2 gene was decreased by methamphetamine in Bax knockout mice, and the gene was overexpressed in Bax wild-type mice. Additionally, we confirmed that Creb, FosB, and c-Fos were related to rewarding effect and Bax using immunohistochemistry.
Ryu
Na Kyung
NK
Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
Yang
Moon Hee
MH
Jung
Min Seok
MS
Jeon
Jeong Ok
JO
Kim
Kee Won
KW
Park
Jong Hoon
JH
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D046228:Microarray Analysis; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012201:Reward; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D018125:Receptors, Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D008694:Methamphetamine