Long-term suppression of methamphetamine-induced c-Fos expression in rat striatum by the injection of c-fos antisense oligodeoxynucleotides absorbed in water-absorbent polymer.
The use of water-absorbent polymer (WAP) as a hydrogel carrier for the slow delivery of antisense oligodeoxynucleotides (ODN) in the brain, was recently developed. In this experiment, 15-mer phosphorothioate ODN, complementary to c-fos gene absorbed in WAP, was injected in the rat striatum. The expression of c-Fos-immunoreactivity induced by methamphetamine (6 mg/kg, intraperitoneally) around the injection site was suppressed until 5 days after injection. Using this method, it was observed that unilateral injection with c-fos antisense ODN into the rat striatum caused robust ipsilateral rotations after methamphetamine challenge 4 days post injection. This method is simple, and the biological and behavioral effects of antisense ODN in WAP can be maintained for several days even after a single injection into the brain.
Semba
Jun'ichi
J
Division of Health Sciences, University of the Air, Chiba, Japan. sembaj@u-air.ac.jp
Wakuta
Maki
M
Suhara
Tetsuya
T
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D004337:Drug Carriers; D015870:Gene Expression / Q000187:drug effects*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007124:Immunoenzyme Techniques; D007267:Injections; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D011108:Polymers; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects
D004337:Drug Carriers; D020319:Oligodeoxyribonucleotides, Antisense; D011108:Polymers; D016760:Proto-Oncogene Proteins c-fos; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008694:Methamphetamine