c-fos antisense generates apomorphine and amphetamine-induced rotation

Area of Science:

• Neuroscience
• Molecular Biology
• Pharmacology

Background:

• The c-fos gene plays a crucial role in neuronal plasticity and response to stimuli.
• Understanding the role of c-fos in dopamine-mediated behaviors is essential for developing therapeutic strategies.

Purpose of the Study:

• To investigate the role of c-fos in amphetamine- and apomorphine-induced behaviors in rats.
• To determine if antisense inhibition of c-fos affects behavioral and biochemical responses to these drugs.

Main Methods:

• Rats were injected with antisense or sense oligonucleotides targeting c-fos in the striatum.
• Following a 10-hour delay, rats received amphetamine or apomorphine injections.
• Behavioral rotation and immunohistochemistry for Fos and Jun B proteins were assessed.

Main Results:

• Antisense oligonucleotide treatment resulted in rotation towards the injected striatum in response to amphetamine and apomorphine.
• Amphetamine-induced expression of c-Fos and Jun B in striatal neurons was significantly inhibited by the antisense oligonucleotide.
• These behavioral and biochemical effects were observed 10 hours after the initial oligonucleotide injection.

Conclusions:

• Inhibition of c-fos via antisense oligonucleotides can modulate dopamine-related behaviors.
• A delayed biochemical alteration in the striatum following c-fos inhibition appears to block drug-induced effects.
• These findings highlight the potential of targeting c-fos for neurological and psychiatric disorders.