Acute nicotine activates c-fos and activity-regulated cytoskeletal associated protein mRNA expression in limbic brain areas involved in the central stress-response in rat pups during a period of hypo-responsiveness to stress.
ABSTRACT In adult rats, acute nicotine, the major psychoactive ingredient in tobacco smoke, stimulates the hypothalamic-pituitary-adrenal axis (HPA), resulting in activation of brain areas involved in stress and anxiety-linked behavior. However, in rat pups the first two postnatal weeks are characterized by hypo-responsiveness to stress, also called the 'stress non-responsive period' (SNRP). Therefore, we wanted to address the question if acute nicotine stimulates areas involved in the stress response during SNRP. To determine neuronal activation, the expression of the immediate-early genes c-fos and activity-regulated cytoskeletal associated protein (Arc) was studied in the central nucleus of the amygdala (CeA), bed nucleus stria terminalis (BST) and paraventricular hypothalamic nucleus (PVN), which are areas involved in the neuroendocrine and central stress response. Rat pups received nicotine tartrate (2 mg/kg) or saline by i.p. injection at postnatal days (P) 5, 7 and 10 and their brains were removed after 30 min. We used semi-quantitative radioactive in situ hybridization with gene specific antisense cRNA probes in coronal sections. In control pups, c-fos expression was low in most brain regions, but robust Arc hybridization was found in several areas including cingulate cortex, hippocampus and caudate. Acute nicotine resulted in significant induction of c-fos expression in the PVN and CeA at P5, P7 and P10, and in the BST at P7 and P10. Acute nicotine significantly induced expression of Arc in CeA at P5, P7 and P10, and in the BST at P10. In conclusion, acute nicotine age dependently activated different brain areas of the HPA axis during the SNRP. After P7, the response was more pronounced and included the BST, suggesting differential maturation of the HPA axis in response to nicotine.
Article: Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory.[show abstract] [hide abstract]
ABSTRACT: It is widely believed that the brain processes information and stores memories by modifying and stabilizing synaptic connections between neurons. In experimental models of synaptic plasticity, such as long-term potentiation (LTP), the stabilization of changes in synaptic strength requires rapid de novo RNA and protein synthesis. Candidate genes, which could underlie activity-dependent plasticity, have been identified on the basis of their rapid induction in brain neurons. Immediate-early genes (IEGs) are induced in hippocampal neurons by high-frequency electrical stimulation that induces LTP and by behavioral training that results in long-term memory (LTM) formation. Here, we investigated the role of the IEG Arc (also termed Arg3.1) in hippocampal plasticity. Arc protein is known to be enriched in dendrites of hippocampal neurons where it associates with cytoskeletal proteins (Lyford et al., 1995). Arc is also notable in that its mRNA and protein accumulate in dendrites at sites of recent synaptic activity (Steward et al., 1998). We used intrahippocampal infusions of antisense oligodeoxynucleotides to inhibit Arc protein expression and examined the effect of this treatment on both LTP and spatial learning. Our studies show that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory. Thus, Arc appears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity.Journal of Neuroscience 07/2000; 20(11):3993-4001. · 7.11 Impact Factor