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Effect of neonatal isolation on the noradrenergic transduction system in the rat hippocampal slice

Numerous studies suggest that early adverse experiences induce neurochemical, morphological, and functional changes in the hippocampus in adolescence and adulthood. The aim of this study was to identify the influence of neonatal isolation (NI) on noradrenaline (NA)‐mediated intracellular calcium ([Ca2+]i) mobilization. To measure [Ca2+]i, we used the Ca2+‐sensitive dye fura‐2 and analysis by fluorescence microscopy. First, we examined the contributions of adrenergic receptor subtypes to the NA‐stimulated increase in [Ca2+]i in the granule cell layers of the dentate gyrus (DG) and in the pyramidal cell layers of the CA3 in the hippocampus. Second, we found that the NA‐stimulated [Ca2+]i increment was significantly decreased in response to NI in these hippocampal regions. In addition, we examined the influence of environmental enrichment (EE) after weaning on the decrease in the NA‐stimulated [Ca2+]i increment induced by NI. The administration of EE reversed the influence of NI on the NA‐stimulated [Ca2+]i increment in the CA3 pyramidal cell layer but not in the DG granular cell layer in the hippocampus. These findings suggest that NI and EE after weaning may modulate hippocampal function by altering adrenergic receptor‐mediated signal transduction during adolescence. Synapse 54:223–232, 2004. © 2004 Wiley‐Liss, Inc.