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 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 day (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.

The influence of adolescent nicotine exposure on ethanol intake and brain gene expression

“…These genes have been implicated in synaptic plasticity [ 115 ] and associated with addiction [ 113 ]. Our results are not consistent with previous research that has reported increased Arc and Fos expression in the prefrontal cortex (PFC) following an acute injection of nicotine in adolescent male rats [ 113 ] and rat pups [ 116 ]. It is possible that we observed a different pattern of gene expression due to the brain region studied.…”

Smoking during pregnancy: lessons learned from epidemiological studies and experimental studies using animal models

“…respectively, which also can be evaluated in animal models (Lara et al�, 2006)� Dysfunction in the monoamine systems, in particularly the noradrenergic, dopamineric and serotonergic systems, has been strongly implicated in affective disorders including anxiety, depression and aggression (van Praag, 1998;Ressler & Nemeroff, 2000;Nutt, 2006;Seo et al�, 2008;Goddard et al�, 2010), and make individuals susceptible to subsequent substance abuse, as well as increase risk of posttraumatic stress disorder, major depressive disorder and suicide� There is strong evidence to suggest that gestational exposure to nicotine affects the development of central monoamineric systems in rodents (Muneoka et al�, 1997;Slotkin et al�, 1987;Oliff & Gallardo, 1999;Xu et al�, 2001)� Furthermore, in young postnatal rat pups, a period that corresponds to the third trimester of human development (Winzer-Serhan, 2008), nicotine specifically activates brain areas involved in the central stress response pathway including the noradrenergic locus coeruleus (Schmitt et al�, 2008)� Thus, it is possible that gestational exposure to nicotine due to maternal smoking affects normal development of monoaminergic transmitter systems, which could constitute a major underlying cause for the affective behavioral abnormalities seen in people whose mother smoked while pregnant�…”

Headache in patients with pituitary adenoma: Clinical and paraclinical findings

“…The relationship between smoking and headache is controversial (28). A possible mechanism of headache in smokers with pituitary adenoma might be based on the central effects of nicotine: Acute exposure to nicotine results in an increase of ACTH, PRL (29) and hGH (30) and in an increase of sleep-onset latency (31). In rats, this influence on the hypothalamus-pituitary adrenal axis and on the control of endogenous rhythms and sleep architecture is mediated by brainstem catecholaminergic neurons with a subsequent noradrenaline release in the hypothalamic paraventricular nucleus (32).…”