c-Fos and ΔFosB expression are differentially altered in distinct subregions of the nucleus accumbens shell in cocaine-sensitized rats

Repeated cocaine administration in rats can lead to sensitization as evidenced by an increased locomotor response to a subsequent exposure (challenge) dose of cocaine even after a drug-free period. Expression of the immediate early gene product, c-Fos, differs among distinct subregions of the nucleus accumbens shell. This would suggest that these subregions may be differentially involved in sensitization. The present study quantified c-Fos- and deltaFosB-immunoreactive nuclei in subterritories of the nucleus accumbens in animals behaviorally sensitized to cocaine. Rats received a sensitization-inducing regimen of cocaine (twice-daily injections of 15 mg/kg i.p. for five consecutive days). Fourteen days following the last injection, rats were given a challenge injection of cocaine (15 mg/kg i.p.), and killed 2 h later. Sections through the nucleus accumbens were processed for tyrosine hydroxylase and either c-Fos or deltaFosB. The number of immunoreactive nuclei was quantified in five subregions of the nucleus accumbens shell: the vertex, arch, cone, intermediate zone and ventrolateral zone, which can be identified by differential histological staining for tyrosine hydroxylase. Repeated cocaine administration resulted in robust sensitization that was associated with more deltaFosB in the vertex, arch, and cone compared with saline-treated controls. As previously reported, c-Fos immunoreactivity was increased in the intermediate zone in cocaine-sensitized rats. deltaFosB was significantly elevated in rats that did not receive a cocaine challenge, attesting to the long half-life of this transcription factor. These results provide further evidence suggesting distinct anatomical neuroadaptations within the nucleus accumbens shell that may play a functional role in psychomotor-stimulant sensitization.