Antisense Technology and its Implications Gene Expression Antisense Technology The Design and Targeting of Antisense ODNs

While many studies have examined the numerous physiological and pharmacological factors which can induce the expression of c-fos and other immediate-early genes, few have examined the consequences of altering their expression pattern. Using antisense oligonucleotides to c-fos, we demonstrate that amphetamine-induced c-fos expression c m be attenuated in vivo, in specific brain regions. This unilateral attenuation of c-fos expression in amphetamine-stimulated animals results in a directed rotational behavior. We show that animals rotate only when they express a difference in Fos-LI between the left and right striatum. The attenuation of Fos-LI by the antisense oligonucleotides appears to be dependent on the c-fos mRNA site h t the antisense oligonucleotides target and the degree of chexnical protection of the oligonucleotide against degradation. The attenuation of Fos-LI and the increase in unilaterally directed rotation are both tirne-and dosedependent. These results demonstrate that manipulating immediate-early gene expression by the direct infusion of antisense oligonucleotides in specific brain regions can have behavioral consequences. Antisense technology is a new and fairly unexplored field, that has the potential to play a significant role in elucidating the role that genes play under a wide variety of circumstances. List of Abbreviations