[Use of the antisense oligonucleotide technique in neuropsychopharmacology research]

The technique using antisense oligonucleotides has been widely used in the study of specific functions of targeted protein molecules. This technique has enabled us to perform experiments which were previously impossible in the field of neuropsychopharmacology. Some chemically modified oligonucleotide analogues (i.e., phosphorothioate, S-oligo), which are relatively nuclease-resistant, are now available. However, the molecular mechanisms of action, pharmacokinetics, and kinetics of cellular uptake of antisense oligonucleotides, have not yet been fully understood. Recently, a number of reports have described the use of antisense oligonucleotides in inhibiting gene expression in the living brain, using intact laboratory animals. In the present article, after a brief discussion of mechanisms of action of antisense oligonucleotides, the methodological aspects of antisense experiments using the "mini osmotic pump" as the oligonucleotide delivery system are reviewed. The choice, design, mode of delivery, and dose are also discussed. In particular, we address the advantages and disadvantages of the antisense oligonucleotide technique as well as the control experiments required. This technique is a powerful method and one of the most important tools in neuropsychopharmacology research.