Striatal cell type-specific overexpression of ΔFosB enhances incentive for cocaine

Christina R. Colby, Kim Whisler, Cathy Steffen, Eric J. Nestler, David W. Self

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

The transcription factor ΔFosB accumulates in substance P-dynorphin-containing striatal neurons with repeated cocaine use. Here, we show that inducible transgenic ΔFosB 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, ΔFosB 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 ΔFosB-overexpressing mice, indicating that ΔFosB 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 ΔFosB 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.

Original languageEnglish (US)
Pages (from-to)2488-2493
Number of pages6
JournalJournal of Neuroscience
Volume23
Issue number6
StatePublished - Mar 15 2003

Fingerprint

Corpus Striatum
Cocaine
Motivation
Self Administration
Reinforcement Schedule
Dynorphins
Substance P
Substance-Related Disorders
Appointments and Schedules
Transcription Factors
Pharmacology
Neurons
Recurrence
Food
Pharmaceutical Preparations

Keywords

  • Addiction
  • Cocaine
  • Craving
  • Nucleus accumbens
  • Reinforcement
  • Reward

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Colby, C. R., Whisler, K., Steffen, C., Nestler, E. J., & Self, D. W. (2003). Striatal cell type-specific overexpression of ΔFosB enhances incentive for cocaine. Journal of Neuroscience, 23(6), 2488-2493.

Striatal cell type-specific overexpression of ΔFosB enhances incentive for cocaine. / Colby, Christina R.; Whisler, Kim; Steffen, Cathy; Nestler, Eric J.; Self, David W.

In: Journal of Neuroscience, Vol. 23, No. 6, 15.03.2003, p. 2488-2493.

Research output: Contribution to journalArticle

Colby, CR, Whisler, K, Steffen, C, Nestler, EJ & Self, DW 2003, 'Striatal cell type-specific overexpression of ΔFosB enhances incentive for cocaine', Journal of Neuroscience, vol. 23, no. 6, pp. 2488-2493.
Colby, Christina R. ; Whisler, Kim ; Steffen, Cathy ; Nestler, Eric J. ; Self, David W. / Striatal cell type-specific overexpression of ΔFosB enhances incentive for cocaine. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 6. pp. 2488-2493.
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