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The Journal of Neuroscience, March 15, 2003, 23(6):2488

Striatal Cell Type-Specific Overexpression of FosB Enhances Incentive for Cocaine

Christina R. Colby¹, Kim Whisler², Cathy Steffen², Eric J. Nestler², and David W. Self²

¹ Division of Molecular Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center, New Haven, Connecticut 06508, and ² Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070

The transcription factor FosB accumulates in substance P-dynorphin-containing striatal neurons with repeated cocaine use. Here, we show that inducible transgenic FosB overexpression in this same striatal cell type facilitates acquisition of cocaine self-administration at low-threshold doses, consistent with increased sensitivity to the pharmacological effects of the drug. Importantly, FosB also enhances the degree of effort mice will exert to maintain self-administration of higher doses on a progressive ratio schedule of reinforcement, whereas levels of cocaine intake are not altered on less demanding fixed-ratio schedules. Acquisition and extinction of behavior reinforced by food pellets is not altered in FosB-overexpressing mice, indicating that FosB does not alter the capacity to learn an instrumental response or cause response perseveration in the absence of reinforcement. These data suggest that accumulation of FosB contributes to drug addiction by increasing the incentive properties of cocaine, an effect that could increase the risk for relapse long after cocaine use ceases.

Key words: cocaine; reinforcement; reward; addiction; nucleus accumbens; craving

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2362488-06$05.00/0

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