Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments.
Following chronic cocaine treatment, we have found a long-lasting increase in AP-1 binding in the rat nucleus accumbens and striatum, two important targets of the behavioral effects of cocaine. This increase develops gradually over several days and remains at 50% of maximal levels 7 days after the last cocaine exposure. Supershift experiments, along with one- and two-dimensional Western blots, indicate that this chronic AP-1 complex contains at least four Fos-related antigens (FRAs), some of which display delta FosB-like immunoreactivity, that are induced selectively by chronic, but not acute, cocaine treatment. The same chronic FRAs were also induced by several different types of chronic treatments in a region-specific manner in the brain. Thus, the chronic FRAs and associated chronic AP-1 complex could mediate some of the long-term changes in gene expression unique to the chronic-treated state as opposed to the acute-treated and normal states.
Hope
B T
BT
Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut.
Nye
H E
HE
Kelz
M B
MB
Self
D W
DW
Iadarola
M J
MJ
Nakabeppu
Y
Y
Duman
R S
RS
Nestler
E J
EJ
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D003042:Cocaine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D015180:Electrophoresis, Gel, Two-Dimensional; D004597:Electroshock; D007526:Isoelectric Point; D008297:Male; D008970:Molecular Weight; D009714:Nucleus Accumbens / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism*; D014191:Tranylcypromine / Q000008:administration & dosage
D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D014191:Tranylcypromine; D003042:Cocaine