Striatal regulation of [Delta]FosB, FosB, and cFos during cocaine self-administration and withdrawal

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 [Delta]FosB, in striatal subregions during and after chronic intravenous cocaine administration in self-administering and yoked rats. We found that cFos, FosB, and [Delta]FosB exhibit regionally and temporally distinct expression patterns, with greater accumulation of [Delta]FosB protein in the nucleus accumbens (NAc) shell and core after chronic cocaine administration, whereas [Delta]FosB increases in the caudate-putamen (CPu) remained similar with either acute or chronic administration. In contrast, tolerance developed to cocaine-induced mRNA for [Delta]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 [Delta]FosB was similar in cocaine self-administering and yoked animals. Thus, [Delta]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 [Delta]FosB in the NAc, could contribute to addiction-related increases in cocaine-seeking behavior. [PUBLICATION ABSTRACT]