ANTISENSE OLIGODEOXYNUCLEOTIDES AS SPECIFIC TOOLS FOR STUDYING NEUROENDOCRINE AND BEHAVIORAL FUNCTIONS - SOME PROSPECTS AND PROBLEMS

Synthetic antisense oligodeoxynucleotides can inhibit the expression o f a gene in a sequence-specific manner at the translational level. The ir potential use to understand the role of neuropeptides or neurotrans mitters in neuroendocrine and behavioral functions, and perhaps for th erapeutic gene suppression, has become of great interest in neuroscien ce, especially in the cases of absence of available specific antagonis ts. Whether their action can be fully specific to the target gene and not only sequence-specific is, however, the main question about their application to brain studies. A number of factors such as the mode of action, specificity and chemistry of antisense molecules as well as th e carrier vehicle and the time course of antisense treatment, must be carefully considered for the design and successful application of anti sense oligonucleotides. Assay systems and controls must be chosen so a s to ensure that the observed biological effects of antisense oligodeo xynucleotides do in fact reflect the result of a specific target gene inhibition. This article discusses these biochemical factors with the emphasis on the use of phosphodiester or phosphorothioate oligodeoxynu cleotides in neuroendocrine or behavioral studies.