C-FOS ANTISENSE GENERATES APOMORPHINE AND AMPHETAMINE-INDUCED ROTATION

SODIUM pentobarbital anaesthetized rats were injected ipsilaterally with an antisense oligonucleotide to c-fos and contralaterally with a sense oligonucleotide to c-fos in the striatum. Ten hours later they were injected with amphetamine or apomorphine and their behaviour was observed for a further 2 h at which time they were overdosed with anaesthetic and their brains were removed, frozen and processed for Fos and Jun B immunohistochemistry. Rats showed amphetamine- and apomorphine-induced rotation towards the antisense injected striatum. The antisense oligonucleotide also strongly inhibited the amphetamine-induced expression of c-Fos and Jun B in striatal neurones. These results suggest that antisense to c-fos produces a biochemical change in the injected striatum that then, 10 h later, blocks amphetamine- and apomorphine-induced behavioural and biochemical effects.