DeltaFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment.
The transcription factor deltaFosB is induced in the nucleus accumbens and dorsal striatum by chronic exposure to several drugs of abuse, and increasing evidence supports the possibility that this induction is involved in the addiction process. However, to date there has been no report of deltaFosB induction by drugs of abuse in the ventral tegmental area (VTA), which is also a critical brain reward region. In the present study, we used immunohistochemistry to demonstrate that chronic forced administration of cocaine induces deltaFosB in the rat VTA. This induction occurs selectively in a gamma-aminobutyric acid (GABA) cell population within the posterior tail of the VTA. A similar effect is seen after chronic cocaine self-administration. Induction of deltaFosB in the VTA occurs after psychostimulant treatment only: it is seen with both chronic cocaine and amphetamine, but not with chronic opiates or stress. The expression of deltaFosB appears to be mediated by dopamine systems, as repeated administration of a dopamine uptake inhibitor induced deltaFosB in the VTA, while administration of serotonin or norepinephrine uptake inhibitors failed to produce this effect. Time course analysis showed that, following 14 days of cocaine administration, deltaFosB persists in the VTA for almost 2 weeks after cocaine withdrawal. This accumulation and persistence may account for some of the long-lasting changes in the brain associated with chronic drug use. These results provide the first evidence of deltaFosB induction in a discrete population of GABA cells in the VTA, which may regulate the functioning of the brain's reward mechanisms.
Perrotti
Linda I
LI
Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA.
Bolaños
Carlos A
CA
Choi
Kwang-Ho
KH
Russo
Scott J
SJ
Edwards
Scott
S
Ulery
Paula G
PG
Wallace
Deanna L
DL
Self
David W
DW
Nestler
Eric J
EJ
Barrot
Michel
M
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders; D007700:Kinetics; D008297:Male; D009020:Morphine / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D014157:Transcription Factors / Q000096:biosynthesis*; D017557:Ventral Tegmental Area / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D003042:Cocaine