THE APPLICATION OF ANTISENSE OLIGONUCLEOTIDE TECHNOLOGY TO THE BRAIN - SOME PITFALLS

1. Amphetamine-induced c-fos and egr-1 expression in the striatum was used as a model in which to study the effects of antisense oligodeoxyn ucleotides (ODNs) directed at c-fos. Using direct infusions of ODNs in to the striata of animals we have demonstrated that c-fos antisense OD Ns retain most of their biological activity with 2- or 3-base substitu tions. The c-fos antisense and mismatch ODNs attenuated Fos immunoreac tivity but had little effect on Egr-1 immunoreactivity. 2. In another group of studies examining the role of c-fos in amygdala kindling, we have demonstrated that ODNs cause neurotoxic damage following repeated daily infusions into the amygdala. The damage observed was greatly di minished when the time interval between infusions was extended.