PUTATIVE ROLES FOR THE INDUCIBLE TRANSCRIPTION FACTOR C-FOS IN THE CENTRAL-NERVOUS-SYSTEM - STUDIES WITH ANTISENSE OLIGONUCLEOTIDES

Although immediate-early genes such as c-fos are widely believed to pl ay an important role in neuroplasticity, there is limited evidence to support involvement in the initiation of molecular events leading to m edium- and long-term changes in brain function following a stimulus. R esults using techniques such as transgenic knockout of the gene are of ten difficult to interpret. Antisense oligonucleotide technology offer s an alternative. Infusion of antisense oligonucleotide to modify the expression of c-fos in the brain results in dramatic changes in rotati on behaviour in animals challenged with psychostimulant drugs such as amphetamine. Similarly, the knockdown of c-fos expression using antise nse oligonucleotides can also alter the rate of amygdala kindling in r esponse to electrical stimulation of the brain. While studies using an tisense oligonucleotides to knockdown c-fos expression provide evidenc e that the expression of c-fos plays an important role in regulating n euronal function, the use of antisense nucleotides has limitations and experiments must be very carefully controlled. Many details of antise nse oligonucleotide actions remain unknown. (C) 1997 Elsevier Science Ltd.