Amphetamine-induced Fos expression is evident in gamma-aminobutyric acid neurons in the globus pallidus and entopeduncular nucleus in rats treated with intrastriatal c-fos antisense oligodeoxynucleotides.
Double immunostaining for Fos and gamma-aminobutyric acid (GABA) was used in a previously established animal model of striatal dysfunction to examine whether GABA-immunoreactive neurons in the globus pallidus (GP) and entopeduncular nucleus (EP) are activated to express Fos immunoreactivity by intraperitoneal injection of amphetamine. Striatal efferent activity was suppressed by intrastriatal infusions of antisense oligodeoxynucleotide targeted to the messenger RNA of the immediate early gene, c-fos. This suppression produced robust rotational behavior and expression of Fos in the ipsilateral GP and EP following amphetamine challenge. The expression of Fos in the ipsilateral GP and EP following amphetamine challenge is not observed in naïve or control antisense-treated animals. Quantitative analysis revealed that a majority of the amphetamine-activated (Fos-immunoreactive) neurons in the GP and EP express GABA. The present results suggest that inhibitory GABAergic projection neurons within these two nuclei are regulated by inhibitory striatal output and suggests that decreased inhibitory striatal output may contribute to the motor dysfunction observed in patients with Huntington's disease.
Ishida
Yasushi
Y
Department of Psychiatry, Miyazaki Medical College, 5200 Kihara, Kiyotake-cho, Miyazaki-gun, Miyazaki, 889-1692, Japan
Denovan-Wright
Eileen
E
Hebb
Matthew O
MO
Robertson
Harold A
HA
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D020392:Entopeduncular Nucleus / Q000166:cytology / Q000378:metabolism*; D005917:Globus Pallidus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D000662:Amphetamines; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid