DISTRIBUTED CHANGES IN C-FOS AND C-JUN IMMUNOREACTIVITY IN THE RAT-BRAIN ASSOCIATED WITH AROUSAL AND HABITUATION TO NOVELTY

The effects of exposure to spatial novelty on expression of the immedi ate early gene (IEG) products c-Fos and c-Jun were mapped in the rat b rain by immunohistochemistry. Adult male Sprague-Dawley rats were test ed for 10 min in a Lat-maze, and comer-crossings, rearings, and fecal boli were recorded. Rats were sacrificed at different time intervals a fter 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. No nperfused brains were processed for immunocytochemistry for c-Fos and c-Jun on adjacent slices using the avidin-biotin method and diaminoben zidine as chromogen. In unexposed control rats the constitutive expres sion 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 re ticular formation, the caudate-putamen complex, the hippocampus (granu lar and pyramidal neurons), the cerebellum (granular neurons), and all layers of somatosensory cortex. The positivity was stronger in rats e xposed for the first time to the box than in repeatedly exposed or une xposed control rats. A maximal IEG expression was found in animals wit h postexposure survival times of 2 and 6 h. IEG expression in repeated ly 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 colocalize d 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 ju n immunoreactivity induced by exposure to spatial novelty suggests tha t information processing associated with such a nonassociative learnin g task takes place at different organizational levels of the CNS as po stulated by the neural network hypothesis.