c-fos antisense blocks methamphetamine-induced ambulatory activity reversibly.
To investigate the involvement of immediate early genes (IEGs) in the ambulatory activity induced by a low dose of methamphetamine (MAP) in mice, we injected an antisense phosphorothioate oligodeoxynucleotide (ODN) to c-fos mRNA stereotactically into the striatum of ddY male mice. MAP (2 mg kg-1)-induced ambulatory activity was significantly suppressed when the mouse was pretreated by the ODN (2 mM, 1 microliter), and this was accompanied by a decrease in c-Fos-like protein immunoreactivity. Repetitive intermittent administration of MAP at intervals of 3 days confirmed that the suppressive effect was transient and reproducible. These results suggest that c-Fos is at least partly the key molecule regulating the psychomotor stimulation by MAP in mouse brain.
Umekage
T
T
Department of Pharmacology, National Defense Medical College, Tokorozawa, Japan.
Namima
M
M
Fukushima
K
K
Sugita
S
S
Watanabe
Y
Y
D000818:Animals; D007150:Immunohistochemistry; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000494:pharmacology*; D014793:Visual Cortex / Q000187:drug effects*
D016760:Proto-Oncogene Proteins c-fos; D008694:Methamphetamine