Distinct patterns of ΔFosB induction in brain by drugs of abuse

Synapse - Tập 62 Số 5 - Trang 358-369 - 2008
Linda I. Perrotti1,2,3, R.R. Weaver3, Barrie D. Robison1,2, William Renthal1,2, Ian Maze1,2, Shiraz Yazdani1,2, R.G. Elmore1,2, Darin J. Knapp4, Dana E. Selley5,6, Billy R. Martin5,6, L. Sim‐Selley5,6, Ryan K. Bachtell1,2, David W. Self1,2, E J Nestler1,2
1Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas
2Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas
3Department of Psychology, College of Science, The University of Texas at Arlington, Arlington, Texas
4Department of Psychiatry, Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
5Department of Pharmacology and Toxicology, Virginia Commonwealth University Medical College of Virginia, Richmond, Virginia
6Institute for Drug and Alcohol Studies, Virginia Commonwealth University Medical College of Virginia, Richmond, Virginia

Tóm tắt

AbstractThe transcription factor ΔFosB 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 ΔFosB 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 Δ9‐tetrahydrocannabinol (Δ9‐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 Δ9‐THC, robustly induces ΔFosB 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 ΔFosB induction in dorsal striatum. In addition, all four drugs induced ΔFosB in prefrontal cortex, with the greatest effects observed with cocaine and ethanol, and all of the drugs induced ΔFosB to a small extent in amygdala. Furthermore, all drugs induced ΔFosB in the hippocampus, and, with the exception of ethanol, most of this induction was seen in the dentate. Lower levels of ΔFosB induction were seen in other brain areas in response to a particular drug treatment. These findings provide further evidence that induction of ΔFosB in nucleus accumbens is a common action of virtually all drugs of abuse and that, beyond nucleus accumbens, each drug induces ΔFosB in a region‐specific manner in brain. Synapse 358–369, 2008. © 2008 Wiley‐Liss, Inc.

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Synapse

Tập 62 Số 5

358-369

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