IMMEDIATE-EARLY GENES AND BRAIN DNA REMODELING IN THE NAPLES HIGH-EXCITABILITY AND LOW-EXCITABILITY RAT LINES FOLLOWING EXPOSURE TO A SPATIAL NOVELTY

The aim of these studies was to map the neural consequences of exposur e to a spatial novelty on the expression of immediate gene (IEG) and o n unscheduled brain DNA synthesis (UBDS) in two genetic models of alte red activity and hippocampal functions, i.e., the Naples High- (NHE) a nd Low-excitability (NLE) rats, Adult male rats of NLE and NHE lines, and of a random-bred stock (NRB) were tested in a Lat-maze, and corner crossings, rearings, and fecal boli were counted during two 10-min te sts 24 h apart. For IEG expression, rats were exposed to a Lat-maze wi th nonexposed or repeatedly exposed rats used as controls, and were sa crificed at different time intervals thereafter. For UBDS, rats were s acrificed immediately after the first or the second exposure o a Lat-m aze. IEG expression was measured by immunocytochemistry for the FOS an d JUN proteins. NRB rats exposed for the first time to the maze showed extensive FOS and JUN positive cells in the reticular formation, the granular and pyramidal neurons of hippocampus, the amygdaloid nuclei, all layers of somatosensory cortex, and the granule cells of the cereb ellar cortex. The positivity, stronger in rats exposed for the first t ime, was present between 2 and 6 h and was prevented by the NMDA recep tor antagonist CPP (5 mg/kg). The positivity was very low in NHE rats, and it was stronger in NLE compared to NRB rats. UBDS was measured in ex vivo homogenates of brain areas by the incorporation into DNA of H -3[methyl]-thymidine given intraventricularly 15 min before test trial 1 or 2 (pulse of 0.5 h). The basal level of UBDS was higher in the hi ppocampus and neostriata of both NLE/NHE compared to NRB rats. On test trial 1 only, there was a significant decrease in UBDS in the neocort ex and hippocampus of the NLE/NHE rats, and in the hypothalamus, midbr ain, and cerebellum of NLE rats only. This decrease was lower in NHE t han in NLE rats. In conclusion, the differential genotype-dependent pr ofile of FOS and JUN peptides and UBDS in the NLE/NHE rats might cast some light on the neural substrates of spatial and emotional informati on processing in these neurogenetic models.