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c-fos antisense blocks methamphetamine-induced ambulatory activity reversibly
T Umekage1, M Namima, K Fukushima
1Department of Pharmacology, National Defense Medical College, Tokorozawa, Japan.
Neuroreport
|January 20, 1997
Summary
Methamphetamine-induced activity in mice is regulated by c-Fos, an immediate early gene. Blocking c-Fos expression with antisense oligodeoxynucleotides (ODN) temporarily reduced this stimulant effect.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Immediate early genes (IEGs) play crucial roles in neuronal plasticity.
- Methamphetamine (MAP) is a psychostimulant known to induce behavioral changes.
Purpose of the Study:
- To investigate the role of c-fos, an IEG, in methamphetamine-induced ambulatory activity in mice.
- To determine if c-Fos is a key mediator of MAP's psychomotor effects.
Main Methods:
- Stereotactic injection of antisense oligodeoxynucleotides (ODN) targeting c-fos mRNA into the striatum of ddY male mice.
- Administration of a low dose of methamphetamine (MAP) (2 mg/kg).
- Assessment of ambulatory activity and c-Fos-like protein immunoreactivity.
Main Results:
- MAP-induced ambulatory activity was significantly suppressed by ODN pretreatment.
- This suppression was associated with a decrease in c-Fos-like protein levels.
- The observed suppressive effect was transient and reproducible upon repeated MAP administration.
Conclusions:
- c-Fos is partially involved in regulating methamphetamine-induced psychomotor stimulation in mice.
- Targeting c-Fos expression may offer a strategy to modulate MAP's behavioral effects.