Distributed changes in c-Fos and c-Jun immunoreactivity in the rat brain associated with arousal and habituation to novelty

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Abstract

The effects of exposure to spatial novelty on expression of the immediate early gene (IEG) products c-Fos and c-Jun were mapped in the rat brain by immunohistochemistry. Adult male Sprague-Dawley rats were tested for 10 min in a Làt-maze, and corner-crossings, rearings, and fecal boli were recorded. Rats were sacrificed at different time intervals after exposure to the maze (0.5, 2, 6, or 24 h). Unexposed rats or rats repeatedly exposed for 3 days at 24 h interval served as controls. Nonperfused brains were processed for immunocytochemistry for c-Fos and c-Jun on adjacent slices using the avidin-biotin method and diaminobenzidine as chromogen. In unexposed control rats the constitutive expression of the two IEGs products was low and scattered. In contrast, rats that had been exposed for the first time to the maze (spatial novelty) showed an extensive c-Fos- and c-Jun-like immunoreactivity in the reticular formation, the caudate-putamen complex, the hippocampus (granular and pyramidal neurons), the cerebellum (granular neurons), and all layers of somatosensory cortex. The positivity was stronger in rats exposed for the first time to the box than in repeatedly exposed or unexposed control rats. A maximal IEG expression was found in animals with postexposure survival times of 2 and 6 h. IEG expression in repeatedly exposed rats was still above baseline expression of unexposed rats but still lower than that of rats having been exposed only once to the maze. The fos and jun-like immunoreactivity appeared to be colocalized in the same neurons and was partially prevented by pretreatment with the competitive NMDA receptor antagonist CPP at a high (5 mg/kg) but not at a low dose (0.1 mg/kg). The widespread induction of fos and jun immunoreactivity induced by exposure to spatial novelty suggests that information processing associated with such a nonassociative learning task takes place at different organizational levels of the CNS as postulated by the neural network hypothesis.

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