Antisense oligonucleotide to c-fos induces ipsilateral rotational behaviour to d-amphetamine

The immediate-early genes, especially c-fos, have been suggested to have an important role in neuronal plasticity and memory. However, it has been difficult to determine if in fact c-fos can participate in control of behaviour. Here we can report that direct unilateral infusion into the rat neostriatum of an antisense phosphothioate oligodeoxynucleotide to c-fos mRNA leads to the rapid induction of ipsilateral rotational behaviour after d-amphetamine administration. This is associated with an elimination of the in vivo expression of Fos-like immunoreactivity within the infused region of neostriatum. Following infusion of these oligodeoxynucleotides labelled with fluorescein isothiocyanate they appear with a nuclear and cytoplasmic location in a large number of nerve cells, many of which are immunoreactive for dopamine and cyclic AMP regulated phosphoprotein. The present findings suggest that the immediate-early gene c-fos has a role also in control of behavioural activity, as illustrated in D1 receptor containing striatal neurones.