Distinct patterns of DeltaFosB induction in brain by drugs of abuse.
The transcription factor DeltaFosB accumulates and persists in brain in response to chronic stimulation. This accumulation after chronic exposure to drugs of abuse has been demonstrated previously by Western blot most dramatically in striatal regions, including dorsal striatum (caudate/putamen) and nucleus accumbens. In the present study, we used immunohistochemistry to define with greater anatomical precision the induction of DeltaFosB throughout the rodent brain after chronic drug treatment. We also extended previous research involving cocaine, morphine, and nicotine to two additional drugs of abuse, ethanol and Delta(9)-tetrahydrocannabinol (Delta(9)-THC, the active ingredient in marijuana). We show here that chronic, but not acute, administration of each of four drugs of abuse, cocaine, morphine, ethanol, and Delta(9)-THC, robustly induces DeltaFosB in nucleus accumbens, although different patterns in the core vs. shell subregions of this nucleus were apparent for the different drugs. The drugs also differed in their degree of DeltaFosB induction in dorsal striatum. In addition, all four drugs induced DeltaFosB in prefrontal cortex, with the greatest effects observed with cocaine and ethanol, and all of the drugs induced DeltaFosB to a small extent in amygdala. Furthermore, all drugs induced DeltaFosB in the hippocampus, and, with the exception of ethanol, most of this induction was seen in the dentate. Lower levels of DeltaFosB induction were seen in other brain areas in response to a particular drug treatment. These findings provide further evidence that induction of DeltaFosB in nucleus accumbens is a common action of virtually all drugs of abuse and that, beyond nucleus accumbens, each drug induces DeltaFosB in a region-specific manner in brain.
Perrotti
L I
LI
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
Weaver
R R
RR
Robison
B
B
Renthal
W
W
Maze
I
I
Yazdani
S
S
Elmore
R G
RG
Knapp
D J
DJ
Selley
D E
DE
Martin
B R
BR
Sim-Selley
L
L
Bachtell
R K
RK
Self
D W
DW
Nestler
E J
EJ
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology; D013287:Illicit Drugs / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
D002492:Central Nervous System Depressants; D006213:Hallucinogens; D013287:Illicit Drugs; D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D000431:Ethanol; D009020:Morphine; D013759:Dronabinol; D003042:Cocaine