Striatal regulation of ΔfosB, FosB, and cFos during cocaine self-administration and withdrawal

Erin B. Larson, Fatih Akkentli, Scott Edwards, Danielle L. Graham, Diana L. Simmons, Imran N. Alibhai, Eric J. Nestler, David W. Self

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Chronic drug exposure induces alterations in gene expression profiles that are thought to underlie the development of drug addiction. The present study examined regulation of the Fos-family of transcription factors, specifically cFos, FosB, and ΔFosB, in striatal subregions during and after chronic intravenous cocaine administration in self-administering and yoked rats. We found that cFos, FosB, and ΔFosB exhibit regionally and temporally distinct expression patterns, with greater accumulation of ΔFosB protein in the nucleus accumbens (NAc) shell and core after chronic cocaine administration, whereas ΔFosB increases in the caudate-putamen (CPu) remained similar with either acute or chronic administration. In contrast, tolerance developed to cocaine-induced mRNA for ΔFosB in all three striatal subregions with chronic administration. Tolerance also developed to FosB expression, most notably in the NAc shell and CPu. Interestingly, tolerance to cocaine-induced cFos induction was dependent on volitional control of cocaine intake in ventral but not dorsal striatal regions, whereas regulation of FosB and ΔFosB was similar in cocaine self-administering and yoked animals. Thus, ΔFosB-mediated neuroadaptations in the CPu may occur earlier than previously thought with the initiation of intravenous cocaine use and, together with greater accumulation of ΔFosB in the NAc, could contribute to addiction-related increases in cocaine-seeking behavior.

Original languageEnglish (US)
Pages (from-to)112-122
Number of pages11
JournalJournal of Neurochemistry
Volume115
Issue number1
DOIs
StatePublished - Oct 2010

Fingerprint

Corpus Striatum
Self Administration
Cocaine
Putamen
Nucleus Accumbens
Transcriptome
Gene expression
Pharmaceutical Preparations
Intravenous Administration
Substance-Related Disorders
Rats
Animals
Transcription Factors
Messenger RNA

Keywords

  • cocaine
  • Fos
  • self-administration
  • striatum
  • withdrawal

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Striatal regulation of ΔfosB, FosB, and cFos during cocaine self-administration and withdrawal. / Larson, Erin B.; Akkentli, Fatih; Edwards, Scott; Graham, Danielle L.; Simmons, Diana L.; Alibhai, Imran N.; Nestler, Eric J.; Self, David W.

In: Journal of Neurochemistry, Vol. 115, No. 1, 10.2010, p. 112-122.

Research output: Contribution to journalArticle

Larson, EB, Akkentli, F, Edwards, S, Graham, DL, Simmons, DL, Alibhai, IN, Nestler, EJ & Self, DW 2010, 'Striatal regulation of ΔfosB, FosB, and cFos during cocaine self-administration and withdrawal', Journal of Neurochemistry, vol. 115, no. 1, pp. 112-122. https://doi.org/10.1111/j.1471-4159.2010.06907.x
Larson, Erin B. ; Akkentli, Fatih ; Edwards, Scott ; Graham, Danielle L. ; Simmons, Diana L. ; Alibhai, Imran N. ; Nestler, Eric J. ; Self, David W. / Striatal regulation of ΔfosB, FosB, and cFos during cocaine self-administration and withdrawal. In: Journal of Neurochemistry. 2010 ; Vol. 115, No. 1. pp. 112-122.
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