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Contains fulltext : 231775.pdf (Publisher’s version ) (Open Access), Extensive evidence indicates that noradrenergic activation is essentially involved in mediating the enhancing effects of emotional arousal on memory consolidation. Our current understanding of the neurobiological mechanisms underlying the memory-modulatory effects of the noradrenergic system is primarily based on pharmacological studies in rats, employing targeted administration of noradrenergic drugs into specific brain regions. However, the further delineation of the specific neural circuitry involved would benefit from experimental tools that are currently more readily available in mice. Previous studies have not, as yet, investigated the effect of noradrenergic enhancement of memory in mice, which show different cognitive abilities and higher endogenous arousal levels induced by a training experience compared to rats. In the present study, we investigated the effect of posttraining noradrenergic activation in male C57BL/6J mice on the consolidation of object recognition and object location memory. We found that the noradrenergic stimulant yohimbine (0.3 or 1.0 mg/kg) administered systemically immediately after an object training experience dose-dependently enhanced 24-h memory of both the identity and location of the object. Thus, these findings indicate that noradrenergic activation also enhances memory consolidation processes in mice, paving the way for a systematic investigation of the neural circuitry underlying these emotional arousal effects on memory.LAY SUMMARY: The current study successfully validated the effect of noradrenergic activation on both object recognition and object location memory in mice. This study thereby provides a fundamental proof-of-principle for the investigation of the neural circuitry underlying noradrenergic and arousal effects on long-term memory in mice.

Contains fulltext : 202805.pdf (publisher's version ) (Closed access)

Item does not contain fulltext, Emotional enhancement of memory by noradrenergic mechanisms is well-described, but the long-term consequences of such enhancement are poorly understood. Over time, memory traces are thought to undergo a neural reorganization, that is, a systems consolidation, during which they are, at least partly, transferred from the hippocampus to neocortical networks. This transfer is accompanied by a decrease in episodic detailedness. Here we investigated whether norepinephrine (NE) administration into the basolateral amygdala after training on an inhibitory avoidance discrimination task, comprising two distinct training contexts, alters systems consolidation dynamics to maintain episodic-like accuracy and hippocampus dependency of remote memory. At a 2-d retention test, both saline- and NE-treated rats accurately discriminated the training context in which they had received footshock. Hippocampal inactivation with muscimol before retention testing disrupted discrimination of the shock context in both treatment groups. At 28 d, saline-treated rats showed hippocampus-independent retrieval and lack of discrimination. In contrast, NE-treated rats continued to display accurate memory of the shock-context association. Hippocampal inactivation at this remote retention test blocked episodic-like accuracy and induced a general memory impairment. These findings suggest that the NE treatment altered systems consolidation dynamics by maintaining hippocampal involvement in the memory. This shift in systems consolidation was paralleled by time-regulated DNA methylation and transcriptional changes of memory-related genes, namely Reln and Pkmzeta, in the hippocampus and neocortex. The findings provide evidence suggesting that consolidation of emotional memories by noradrenergic mechanisms alters systems consolidation dynamics and, as a consequence, influences the maintenance of long-term episodic-like accuracy of memory.

BACKGROUND: International guidelines recommend systematic assessment of pain, agitation/sedation and delirium with validated scales for all ICU patients. However, these evaluations are often not done. We have created an e-learning training platform for the continuous medical education, and assessed its efficacy in increasing the use of validated tools by all medical and nursing staff of the participating ICUs during their daily practice. METHODS: Multicenter, randomized, before and after study. The eight participating centers were randomized in two groups, and received training at different times. The use of validated tools (Verbal Numeric Rating or Behavioral Pain Scale for pain; Richmond Agitation-Sedation Scale for agitation; Confusion Assessment Method for the ICU for delirium) was evaluated from clinical data recorded in medical charts during a week, with follow-up up to six months after the training. All the operators were invited to complete a questionnaire, at baseline and after the training. RESULTS : Among the 374 nurses and physicians involved, 140 (37.4%) completed at least one of the three courses. The assessment of pain (38.1 vs. 92.9%, P<0.01) and delirium (0 vs. 78.6%, P<0.01) using validated tools significantly increased after training. Observation in the follow-up showed further improvement in delirium monitoring, with no signs of extinction for pain and sedation/agitation measurements. CONCLUSIONS: This e-learning program shows encouraging effectiveness, and the increase in the use of validated tools for neurological monitoring in critically ill patients lasts over time.

Psychiatric disorders and in particular depression have increased during the "Great Recession". The aim of this study was to investigate the consumption of psychotropic drugs in people who lost their permanent employment, using administrative data. The study considered all of the subjects domiciled in Lombardy, Northern Italy, who lost a permanent employment between 2008 and 2010, not assuming psychotropic drugs and who did not find a new job within the following 12 months. The control group included people who did not lose permanent job in the study period, matched to the cases for gender, age, nationality, skill level, education and economic sector, using propensity score matching. The subjects who lost their permanent employment were 17 % more likely to receive one or more drug prescriptions than the controls, but the difference was significant only for males. Females, subjects aged > 50 years, low skill level workers and Italians were more likely to have received a prescription for psychotropic drugs than respectively males, subjects aged 20-29 years or aged 30-39 years, low skill level workers and non-Italians. The average number of drugs prescribed for those who lost their job and those who continued working was respectively 2.9 and 3.1. In conclusion, losing a permanent job increases significantly psychotropic drugs consumption in males but not in females

Item does not contain fulltext, Increased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats previously exposed to traumatic stress showing inconsistent results. The aim of this study was to investigate the effects of an inescapable foot shock (IFS) procedure (1) on reactivity to novelty in an open-field (as an index of hyperarousal), and (2) on noradrenaline release in the amygdala during an acute stress. To test the role of noradrenaline in amygdala, we also investigated the effects of microinjections of propranolol, a beta-adrenoreceptor antagonist, and clenbuterol, a beta-adrenoreceptor agonist, into the amygdala of IFS and control animals. Finally, we evaluated the expression of mRNA levels of beta-adrenoreceptors (beta1 and beta2) in the amygdala, the hippocampus and the prefrontal cortex. Male Wistar rats (3 months) were stereotaxically implanted with bilateral guide cannulae. After recovering from surgery, animals were exposed to IFS (10 shocks, 0.86mA, and 6s per shock) and seven days later either microdialysis or microinjections were performed in amygdala. Animals exposed to IFS showed a reduced locomotion compared to non-shocked animals during the first 5min in the open-field. In the amygdala, IFS animals showed an enhanced increase of noradrenaline induced by stress compared to control animals. Bilateral microinjections of propranolol (0.5mug) into the amygdala one hour before testing in the open-field normalized the decreased locomotion observed in IFS animals. On the other hand, bilateral microinjections of clenbuterol (30ng) into the amygdala of control animals did not change the exploratory activity induced by novelty in the open field. IFS modified the mRNA expression of beta1 and beta2 adrenoreceptors in the prefrontal cortex and the hippocampus. These

Over recent years, there has been a noticeable increase in the prescription of psychotropic drugs (PDs), particularly antidepressants (ADs). The aim of this retrospective study was to evaluate the consumption of PDs by all adult employees in Lombardy aged >18 years in the period 2007-2011 and the possible changes induced by the “economic crisis” in this highly productive area of Italy. The subjects were classified by gender, age class, nationality, education and province. During the five-year period, there were 3,554,860 employed adults in Lombardy, of whom 277,865 (7.8%) used PDs. The use of PDs (particularly ADs) was associated with being an Italian woman aged >55 years with a basic education and a blue collar job. The lower prevalence in immigrants may be due to the difficulty in gaining access to health services. The increase in PD use can be attributed more specifically to ADs and anti-epileptic drugs with anxiolytic properties. Although continuously increasing, the use of AD fluctuated and was greater during the fall and winter. The increase involved all of the provinces in Lombardy in a similar manner. In 39% of cases, the use of PDs (and particularly ADs) was limited to one trimester, although the AD guidelines suggest at least 6-12 months of treatment.

The interpretation of cardiac troponin results has become challenging because of the availability of highly sensitive troponin assays able to detect even small cardiac damage. To investigate whether the highly sensitive cardiac troponin T assay (hs-cTnT) improves early AMI detection, a comparative evaluation between hs-cTnT and the 4th generation assay (4th-cTnT) was performed. Patients who presented to the Emergency Department from June to September 2011 with chest pain were recruited. Blood samples were taken at admission (T0), 1 (T1), 3, 6 and 12 h after presentation and were analysed by 4th-cTnT and hs-cTnT using Modular SWA E170 analyzer (Roche Diagnostics). For this study, only samples at T0 and T1 were evaluated. Of the 386 patients recruited, 32 (8.3%) had AMI. The sensitivity of hs-cTnT at T0 was 72% vs. 50% of 4th-cTnT. In T1 samples the sensitivity of hs-cTnT (97%) was slightly higher than 4th-cTnT (78%) (P=0.06). Our preliminary results showed that hs-cTnT can detect AMI 1 h after the hospital arrival in the majority of patients. Ongoing studies will define best algorithms for the effective use of hs-cTnT results in clinical practice. Rule-out and rule-in algorithms will have to be fine tuned to exploit cost-savings associated with this early diagnostic accuracy.