Abstract

The aim of these studies was to map the neural consequences of exposure to a spatial novelty on the expression of immediate gene (IEG) and on unscheduled brain DNA synthesis (UbDS) in two genetic models of altered activity and hippocampal functions, i.e., the Naples High- (NHE) and Low-excitability (NLE) rats. Adult male rats of NLE and NHE lines, and of a random-bred stock (NRB) were tested in a Làt-maze, and corner crossings, rearings, and fecal boll were counted during two 10-min tests 24 h apart. For IEG expression, rats were exposed to a Làt-maze with nonexposed or repeatedly exposed rats used as controls, and were sacrificed at different time intervals thereafter. For UBDS, rats were sacrificed immediately after the first or the second exposure o a Làt-maze. IEG expression was measured by immunocytochemistry for the FOS and 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 cerebellar cortex. The positivity, stronger in rats exposed for the first time, was present between 2 and 6 h and was prevented by the NMDA receptor 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 3H-[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 hippocampus and neostriata of both NLE/NHE compared to NRB rats. On test trial 1 only, there was a significant decrease in UBDS in the neocortex and hippocampus of the NLE/NHE rats, and in the hypothalamus, midbrain, and cerebellum of NLE rats only. This decrease was lower in NHE than in NLE rats. In conclusion, the differential genotype-dependent profile of FOS and JUN peptides and UBDS in the NLE/NHE rats might cast some light on the neural substrates of spatial and emotional information processing in these neurogenetic models.

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