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pubmed:abstractText |
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 ?FosB, in striatal subregions during and after chronic intravenous cocaine administration in self-administering and yoked rats. We found that cFos, FosB, and ?FosB exhibit regionally and temporally distinct expression patterns, with greater accumulation of ?FosB protein in the nucleus accumbens (NAc) shell and core after chronic cocaine administration, whereas ?FosB increases in the caudate-putamen (CPu) remained similar with either acute or chronic administration. In contrast, tolerance developed to cocaine-induced mRNA for ?FosB 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 ?FosB was similar in cocaine self-administering and yoked animals. Thus, ?FosB-mediated neuroadaptations in the CPu may occur earlier than previously thought with the initiation of intravenous cocaine use and, together with greater accumulation of ?FosB in the NAc, could contribute to addiction-related increases in cocaine-seeking behavior.
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