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Abstract Aim Cessation of smoking induces nicotine withdrawal symptoms such as anxiety, depression, and dysphoria, which could lead to smoking relapse. In the present study, we examined the role of noradrenergic transmission within the ventral bed nucleus of the stria terminalis (vBNST) on nicotine withdrawal‐induced aversive behavior. Methods Nicotine dependence in rats was established by subcutaneous implantation with a nicotine‐filled osmotic minipump on day 1. Nicotine withdrawal was precipitated by administration of the nicotine receptor antagonist, mecamylamine (3.0 mg/kg, s.c.), on day 15. Nicotine withdrawal‐induced intra‐vBNST noradrenaline release and aversive behavior were examined by in vivo microdialysis and a conditioned place aversion (CPA) test, respectively. Results Intra‐vBNST noradrenaline release was significantly increased during nicotine withdrawal. Nicotine withdrawal induced aversive behavior, which was attenuated by intra‐vBNST injection of the β‐adrenoceptor antagonist, timolol. Conclusions These results suggest that enhanced noradrenergic transmission via β‐adrenoceptors in the vBNST plays a crucial role in nicotine withdrawal‐induced aversive behavior.

Abstract Aim Our previous studies showed that exposure to acute restraint stress enhanced cocaine‐induced conditioned place preference (cocaine‐CPP) and suggested the possibility that co‐activation of adrenergic transmission boosts the increase in medial prefrontal cortex (mPFC) neuronal activity by the activation of dopaminergic transmission. To examine this possibility, the effects of the co‐treatment with dopamine (DA) and noradrenaline (NA) on mPFC neurons were compared with those of treatment with DA alone using whole‐cell patch‐clamp recordings. Methods The effects of DA alone and a mixture of DA and NA on the membrane potentials and spontaneous excitatory postsynaptic currents (sEPSCs) were examined by electrophysiological recordings of mPFC pyramidal neurons in brain slices of male Sprague Dawley rats. Extracellular DA and NA levels in the mPFC during and after restraint stress exposure were also examined by in vivo microdialysis. Results Dopamine significantly produced depolarizing effects on mPFC neurons and tended to increase sEPSC frequency. Co‐administration of NA with DA produced stronger depolarizing effects and significantly increased sEPSC frequency. The findings suggest that the additional depolarizing effect of NA on DA‐responsive neurons, rather than the excitation of DA‐nonresponsive neurons by NA, contributes to the stronger effect of co‐treatment of NA with DA. Conclusion The present study suggests that NA released by restraint stress exposure cooperates with DA to stimulate DA‐responsive neurons in the mPFC, thereby causing the stress‐induced enhancement of cocaine‐CPP.

The burden of neonatal mortality remains high worldwide, particularly in South Asia. Verbal Autopsy is a method used to identify cause of death (COD) where vital registration capabilities are lacking. This study examines the causes of neonatal mortality in a large study population in rural Southern Nepal. The data used is from a larger cluster-randomized community-based trial. The study includes 984 neonatal deaths with complete verbal autopsy information which occurred between 2010 and 2017. The InterVA-5 software was used to identify COD. COD included severe infection (sepsis, pneumonia, meningitis/encephalitis), intrapartum related events (identified as birth asphyxia), congenital malformations, and other. The neonatal mortality rate was 31.2 neonatal deaths per 1000 live births. The causes of neonatal mortality were identified as prematurity (40%), intrapartum related events (35%), severe infection (19%), congenital abnormalities (4%), and other (2%). A high proportion, 42.5% of neonatal deaths occurred in the first 24 hours after birth. Over half (56.4%) of deaths occurred at home. This large prospective study identifies population level neonatal causes of death in rural Southern Nepal, which can contribute to national and regional COD estimates. Interventions to decrease neonatal mortality should focus on preventative measures and ensuring the delivery of high risk infants at a healthcare facility in the presence of a skilled birth attendant., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Saya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Global DNA methylation was assessed by high-performance liquid chromatography (HPLC) for the first time in Eucalyptus urophylla×Eucalyptus grandis shoot tips comparing three outdoor and one in vitro sources of related genotypes differing in their physiological age. The DNA methylation levels found were consistent with those reported for other Angiosperms using the same HPLC technology. Notwithstanding noticeable time-related fluctuations within each source of plant material, methylation rate was overall higher for the mature clone (13.7%) than for the rejuvenated line of the same clone (12.6%) and for the juvenile offspring seedlings (11.8%). The in vitro microshoots of the mature clone were less methylated (11.3%) than the other outdoor origins, but the difference with the juvenile seedlings was not significant. Immunofluorescence investigations on shoot apices established that the mature source could be distinguished from the rejuvenated and juvenile origins by a higher density of cells with methylated nuclei in leaf primordia. Shoot apical meristems (SAMs) from the mature clone also showed a greater proportion and more methylated cells than SAMs from the rejuvenated and juvenile origins. The nuclei of these latter were characterized by fewer and more dispersed labeled spots than for the mature source. Our findings establish that physiological ageing induced quantitative and qualitative variations of DNA methylation at shoot tip, SAM and even cellular levels. Overall this DNA methylation increased with maturation and conversely decreased with rejuvenation to reach the lower scores and to show the immunolabeling patterns that characterized juvenile material nuclei., (Copyright © Physiologia Plantarum 2011.)