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Background: Following COVID-19 and the lockdowns, maternity care and support for women after delivery have been temporary restructured. Studies show that COVID-19 adversely impacts pregnant and peripartum women in the general population, but experiences among women in the first year after delivery/in the wider postpartum period remain unexplored. Moreover, experiences among women with recent gestational diabetes mellitus (GDM) are lacking; though it is a group with a potential high need for support after delivery. The aim of our study was to investigate (i) how women with recent GDM experienced COVID-19 and the first lockdown in Denmark, and (ii) the women's risk perception and health literacy in terms of interaction with the healthcare system in relation to COVID-19.Methods: We performed a qualitative study among 11 women with recent GDM (infants aged 2-11 months old). Semi-structured interviews were conducted in April-May 2020 by telephone or Skype for Business, when Denmark was under lockdown. We analysed data using a thematic qualitative content analysis.Results: Three themes emerged: i) Everyday life and family well-being, ii) Worries about COVID-19 and iii) Health literacy: Health information and access to healthcare. The women were generally not worried about their own or their infant's risk of COVID-19. The lockdown had a negative impact on everyday life e.g. routines, loneliness, breastfeeding uncertainties and worries for the infant's social well-being; but better family dynamics were also described. It was challenging to maintain healthy behaviours and thus the women described worries for the risk of type 2 diabetes and GDM in subsequent pregnancies. The women missed peer support and face-to-face visits from health visitors and found it difficult to navigate the restructured care with online/telephone set-ups.Conclusions: COVID-19 and the lockdown affected everyday life among women with recent GDM both positively and negatively. Our findings suggest a need for care that are responsive to psychological and social aspects of health throughout the COVID-19 pandemic and support to limit worries about adaptation to motherhood and the infant's social well-being. Communication focusing on the importance and relevance of contacting healthcare providers should also be strengthened. [ABSTRACT FROM AUTHOR]

Background: Understanding individual health literacy needs is crucial when designing supportive and effective health care. However, tools assessing health literacy in practice are lacking. The Conversational Health Literacy Assessment Tool (CHAT) was recently developed, but its ability to assess health literacy remains unexplored. We aimed to investigate the implementation and adoption of CHAT, its ability to increase awareness of health literacy among healthcare providers, and if CHAT could assess health literacy needs in patients. Methods: We performed a qualitative feasibility study of CHAT among healthcare providers (nurses, physiotherapists and occupational therapists) who provide rehabilitation services for patients with noncommunicable diseases in a municipal healthcare centre in Denmark. The study used the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation and Maintenance) to structure interview guide and analysis. We collected qualitative data from four small focus groups with healthcare providers (n = 11). The data were analysed using a deductive thematic three-step method for organising and interpreting data. All informants provided written informed consent prior to data collection. Results: CHAT seems to be a feasible and efficient tool for assessing health literacy needs among individuals with different socio-demographic characteristics and with different diagnoses. CHAT was easiest implemented and adopted by healthcare providers, who were already familiarly with the concept of health literacy. The informants emphasised that an introduction to CHAT and health literacy as concept was valuable for the adoption. Some of them felt frustrated that they did not have opportunity and options to meet the health literacy needs identified by CHAT. Conclusions: CHAT is a promising tool for assessing individual health literacy needs and increasing awareness of health literacy among healthcare providers. For successfully implementation of CHAT, we recommend developing a structured implementation programme, including an introduction to health literacy and an outline of the options for acting upon CHAT results. [ABSTRACT FROM AUTHOR]

Accumulation of aggregated alpha-synuclein (α-syn) is believed to play a pivotal role in the pathophysiology of Parkinson's disease (PD) and other synucleinopathies. As a key constituent of Lewy pathology, more than 90% of α-syn in Lewy bodies is phosphorylated at serine-129 (pS129) and hence, it is used extensively as a marker for α-syn pathology. However, the exact role of pS129 remains controversial and the kinase(s) responsible for the phosphorylation have yet to be determined. In this study, we investigated the effect of Polo-like kinase 2 (PLK2) inhibition on formation of pS129 using an ex vivo organotypic brain slice model of synucleinopathy. Our data demonstrated that PLK2 inhibition has no effect on α-syn aggregation, pS129 or inter-neuronal spreading of the aggregated α-syn seen in the organotypic slices. Instead, PLK2 inhibition reduced the soluble pS129 level in the nuclei. The same finding was replicated in an in vivo mouse model of templated α-syn aggregation and in human dopaminergic neurons, suggesting that PLK2 is more likely to be involved in S129-phosphorylation of the soluble physiological fraction of α-syn. We also demonstrated that reduction of nuclear pS129 following PLK2 inhibition for a short time before sample collection improves the signal-to-noise ratio when quantifying pS129 aggregate pathology. [ABSTRACT FROM AUTHOR]

Here we describe the use of an organotypic hippocampal slice model for studying α-synuclein aggregation and inter-neuronal spreading initiated by microinjection of pre-formed α-synuclein fibrils (PFFs). PFF injection at dentate gyrus (DG) templates the formation of endogenous α-synuclein aggregates in axons and cell bodies of this region that spread to CA3 and CA1 regions. Aggregates are insoluble and phosphorylated at serine-129, recapitulating Lewy pathology features found in Parkinson's disease and other synucleinopathies. The model was found to favor anterograde spreading of the aggregates. Furthermore, it allowed development of slices expressing only serine-129 phosphorylation-deficient human α-synuclein (S129G) using an adeno-associated viral (AAV) vector in α-synuclein knockout slices. The processes of aggregation and spreading of α-synuclein were thereby shown to be independent of phosphorylation at serine-129. We provide methods and highlight crucial steps for PFF microinjection and characterization of aggregate formation and spreading. Slices derived from genetically engineered mice or manipulated using viral vectors allow testing of hypotheses on mechanisms involved in the formation of α-synuclein aggregates and their prion-like spreading. [ABSTRACT FROM AUTHOR]

This study presents an approach making drinking water quality data from the Danish national geodatabase Jupiter available for epidemiological studies on long-term health effects of drinking water quality. Drinking water quality was assigned to all Danish households using spatial methods, and the related uncertainty due to sampling density was identified. Nitrate was used as an example contaminant. From 1978, 98% of all Danish households were geocoded with their precise location, yielding a total of 69 million evaluated household-years. Households supplied by a private well (4% of all household-years) were identified; the remaining majority was supplied by public waterworks. Water supply areas were connected to the Jupiter geodatabase to estimate drinking water quality at publicly supplied households. For privately supplied households, the exposure estimate had a substantially higher uncertainty, with 52% of household-years never being sampled, compared with 1% of publicly supplied household-years. For the 18% of all household-years with no nitrate samples, concentrations were estimated by interpolation and an uncertainty score based on the closest nitrate measurement was introduced. While nitrate was used as an example contaminant, the proposed approach is generic and can be used for all monitored drinking water parameters, after preprocessing and validation of the specific data and assumptions. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic hepatitis B virus infection (CHB) usually mount a modest T cell response against HBV epitopes. In order to determine immunogenic epitopes of HBV recognized by HBV-specific T cells, previous studies focused on previously confirmed HBV epitopes and assessed the T cell response by the number of HBV-specific T cells by IFN-γ ELISPOT. Methods: We studied T cell functionality by combined in silico methods predicting HBV-specific epitopes and experimental investigations on the recognition of these epitopes. 30 chronic CHB patients and 10 patients with resolved HBV (RHB) were included in the study. We identified epitopes from the literature and by in silico analysis. These were evaluated for immunogenicity by use of synthetic peptides representing the epitopes through exposure to PBMCs from patients with CHB or RHB by IFN-γ ELISPOT. The number of IFN-γ producing cells (SFC), mean spot size (MSS) and stimulation index (SI) were recorded. Results: The frequency of HBV-specific T cells producing IFN-γ after stimulation with HBV epitopes was similar in CHB and RHB patients. CHB patients had a higher MSS SI than RHB patients. Patients not carrying the HLA-A2 genotype had higher SFC SI and MSS SI. Patients with HLA-A11 had higher MSS SI compared to non- HLA-A11 allele patients. HBeAg-positive patients had a lower MSS SI, and none of the HBeAg positive patients had the HLA-A11 genotype. We found 3 immunogenic epitopes not described previously. Conclusion: IFN-γ ELISPOT-determined MSS is an efficient marker for T cell recognition of epitopes. This experimental measure showed the in silico analysis for epitope prediction to be a valuable tool in future studies on HLA genotypes and HBV epitopes. This way our study now points to previously unappreciated consequences of carrying the HLA-A11 allele in terms of stronger immunity to HBV. [ABSTRACT FROM AUTHOR]

Objective. Most knowledge about chronic hepatitis B virus (HBV) infection is based upon studies in high-endemic areas with one or two predominant genotype(s). The aim of the study was to describe clinical characteristics of a heterogeneous genotypic HBV patient population in a low-endemic European country. Methods. Data from HBV patients currently followed in a Danish university hospital and affiliated regional clinics were reviewed in accordance to genotype status. Results. Of 540 HBV patients, 462 (86%) were of non-Danish ethnicity originating from 43 different countries. HBV genotype was known in 37% of the patients: A (11%), B (25%), C (25%), D (37%) and E (2%). Logistic regression analysis of pre-treatment data among genotype A-D patients receiving nucleos(t)ide analogue (NA) therapy revealed a decreased HBeAg rate by age (OR = 0.93; CI: 0.89-0.97; p < 0.01) and an increased rate in genotype C patients (OR = 20.5; CI: 3.3-129; p < 0.01). Among untreated patients HBeAg rate was also significantly decreased by age (OR = 0.90 (0.85:0.95; p < 0.0001), whereas the rate was increased in both genotype B and C patients (OR = 7.5; CI: 1.8-30.5; p < 0.01 and OR = 12.2; CI: 3.2-46.6; p < 0.001, respectively). No significant variation was found in HBV DNA level in any of the two groups when adjusting for age, gender, genotype and HBeAg. Increased liver pathology prevalence was, irrespectively of treatment status, associated to age and male gender, but not to any genotype. Conclusion. In this study population, genotype B and C was found associated with higher HBeAg rate but not with increased liver pathology. [ABSTRACT FROM AUTHOR]

Summary: Monocytes play important roles in the inflammatory response, which is essential for the innate response to pathogens. Monocytes are able to differentiate to dendritic cells (DCs) under inflammatory situations. In recent decades, the heterogeneity of monocytes and their different traffic pathways have been identified in both human and murine systems. Different monocyte subsets show distinct inflammatory cytokine profiles and differentiation potential under steady-state and inflammatory situations. We discuss the biology of monocytes, their relationship with DCs, and the potential of monocyte-derived dendritic cells (moDCs) in the design of vaccines against certain chronic infectious diseases. [ABSTRACT FROM AUTHOR]

Transfer of full-length genes including regulatory elements has been the preferred gene therapy strategy for clinical applications. However, with significant drawbacks emerging, targeted gene alteration (TGA) has recently become a promising alternative to this method. By means of TGA, endogenous DNA repair pathways of the cell are activated leading to specific genetic correction of single-base mutations in the genome. This strategy can be implemented using single-stranded oligodeoxyribonucleotides (ssODNs), small DNA fragments (SDFs), triplexforming oligonucleotides (TFOs), adeno-associated virus vectors (AAVs) and zinc-finger nucleases (ZFNs). Despite difficulties in the use of TGA, including lack of knowledge on the repair mechanisms stimulated by the individual methods, the field holds great promise for the future. The objective of this review is to summarize and evaluate the different methods that exist within this particular area of human gene therapy research. [ABSTRACT FROM AUTHOR]

α-Synuclein (α-syn) phosphorylation at serine 129 (pS129-α-syn) is substantially increased in Lewy body disease, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the pathogenic relevance of pS129-α-syn remains controversial, so we sought to identify when pS129 modification occurs during α-syn aggregation and its role in initiation, progression and cellular toxicity of disease. Using diverse aggregation assays, including real-time quaking-induced conversion (RT-QuIC) on brain homogenates from PD and DLB cases, we demonstrated that pS129-α-syn inhibits α-syn fibril formation and seeded aggregation. We also identified lower seeding propensity of pS129-α-syn in cultured cells and correspondingly attenuated cellular toxicity. To build upon these findings, we developed a monoclonal antibody (4B1) specifically recognizing nonphosphorylated S129-α-syn (WT-α-syn) and noted that S129 residue is more efficiently phosphorylated when the protein is aggregated. Using this antibody, we characterized the time-course of α-syn phosphorylation in organotypic mouse hippocampal cultures and mice injected with α-syn preformed fibrils, and we observed aggregation of nonphosphorylated α-syn followed by later pS129-α-syn. Furthermore, in postmortem brain tissue from PD and DLB patients, we observed an inverse relationship between relative abundance of nonphosphorylated α-syn and disease duration. These findings suggest that pS129-α-syn occurs subsequent to initial protein aggregation and apparently inhibits further aggregation. This could possibly imply a potential protective role for pS129-α-syn, which has major implications for understanding the pathobiology of Lewy body disease and the continued use of reduced pS129-α-syn as a measure of efficacy in clinical trials. [ABSTRACT FROM AUTHOR]

Summary: In this systematic review and realist synthesis, we aimed to identify strategies to improve dietary and physical activity behaviors for parents with small children. A systematic literature search was conducted in MEDLINE, Embase, CINAHL, and PsycINFO in July 2021. Included studies had to: (i) target one or both parents with at least one child (0–3 years), (ii) aim to improve diet and physical activity, and (iii) report on diet and physical activity outcomes. Intervention context, delivery, and outcomes were extracted, and behavior change techniques were coded. A program theory was developed, and context‐mechanism‐outcome configurations were identified. In total, 17 interventions reported in 28 studies (19 effectiveness studies; nine protocols) were included. Nine interventions showed small improvements: in diet (n = 5), physical activity (n = 2), or both (n = 2) in mothers. The realist synthesis revealed three strategies to improve health behaviors: (1) using knowledge and role modelling to improve family dynamics, (2) providing various home‐based activities to change home environment, and (3) offering flexible delivery, for example, phone or website‐based to increase social support. Future interventions for parents with small children should consider involving the whole family, focusing on home‐based and practical components, and offering various delivery modes. The protocol for the systematic review and realist synthesis was registered in Research Registry (registration ID: reviewregistry860) March 30th, 2020. [ABSTRACT FROM AUTHOR]

Background: Women with prior gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes; however, this risk can be reduced by engaging in positive health behaviours e.g. healthy diet and regular physical activity. As such behaviours are difficult to obtain and maintain there is a need to develop sustainable behavioural interventions following GDM. We aimed to report the process of systematically developing a health promotion intervention to increase quality of life and reduce diabetes risk among women with prior GDM and their families. We distil general lessons about developing complex interventions through co-production and discuss our extensions to intervention development frameworks.Methods: The development process draws on the Medical Research Council UK Development of complex interventions in primary care framework and an adaptation of a three-stage framework proposed by Hawkins et al. From May 2017 to May 2019, we iteratively developed the Face-it intervention in four stages: 1) Evidence review, qualitative research and stakeholder consultations; 2) Co-production of the intervention content; 3) Prototyping, feasibility- and pilot-testing and 4) Core outcome development. In all stages, we involved stakeholders from three study sites.Results: During stage 1, we identified the target areas for health promotion in families where the mother had prior GDM, including applying a broad understanding of health and a multilevel and multi-determinant approach. We pinpointed municipal health visitors as deliverers and the potential of using digital technology. In stage 2, we tested intervention content and delivery methods. A health pedagogic dialogue tool and a digital health app were co-adapted as the main intervention components. In stage 3, the intervention content and delivery were further adapted in the local context of the three study sites. Suggestions for intervention manuals were refined to optimise flexibility, delivery, sequencing of activities and from this, specific training manuals were developed. Finally, at stage 4, all stakeholders were involved in developing realistic and relevant evaluation outcomes.Conclusions: This comprehensive description of the development of the Face-it intervention provides an example of how to co-produce and prototype a complex intervention balancing evidence and local conditions. The thorough, four-stage development is expected to create ownership and feasibility among intervention participants, deliverers and local stakeholders.Trial Registration: ClinicalTrials.gov NCT03997773 , registered retrospectively on 25 June 2019. [ABSTRACT FROM AUTHOR]

Pain is a common non-motor symptom of Parkinson's disease (PD), with current limited knowledge of its pathophysiology. Here, we show that peripheral inoculation of mouse alpha-synuclein (α-Syn) pre-formed fibrils, in a transgenic mouse model of PD, elicited retrograde trans-synaptic spreading of α-Syn pathology (pSer129) across sensory neurons and dorsal nerve roots, reaching central pain processing regions, including the spinal dorsal horn and the projections of the anterolateral system in the central nervous system (CNS). Pathological peripheral to CNS propagation of α-Syn aggregates along interconnected neuronal populations within sensory afferents, was concomitant with impaired nociceptive response, reflected by mechanical allodynia, reduced nerve conduction velocities (sensory and motor) and degeneration of small- and medium-sized myelinated fibers. Our findings show a link between the transneuronal propagation of α-Syn pathology with sensory neuron dysfunction and neuropathic impairment, suggesting promising avenues of investigation into the mechanisms underlying pain in PD. [ABSTRACT FROM AUTHOR]

Pain is a common non-motor symptom of Parkinson's disease (PD), with current limited knowledge of its pathophysiology. Here, we show that peripheral inoculation of mouse alpha-synuclein (α-Syn) pre-formed fibrils, in a transgenic mouse model of PD, elicited retrograde trans-synaptic spreading of α-Syn pathology (pSer129) across sensory neurons and dorsal nerve roots, reaching central pain processing regions, including the spinal dorsal horn and the projections of the anterolateral system in the central nervous system (CNS). Pathological peripheral to CNS propagation of α-Syn aggregates along interconnected neuronal populations within sensory afferents, was concomitant with impaired nociceptive response, reflected by mechanical allodynia, reduced nerve conduction velocities (sensory and motor) and degeneration of small- and medium-sized myelinated fibers. Our findings show a link between the transneuronal propagation of α-Syn pathology with sensory neuron dysfunction and neuropathic impairment, suggesting promising avenues of investigation into the mechanisms underlying pain in PD. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate whether coping strategies in adolescence (14–15 years of age) were associated with labour-market participation (LMP) in young adulthood (25–26 years of age) and whether the association differed by sex. Methods: A birth cohort from the former county of Ringkjoebing, Denmark, consisting of 2826 individuals, comprised the study population. In 2004, the study population completed a questionnaire from which information about coping and covariates were gathered. Coping strategies were measured using five sub-scales of the Brief COPE Scale, which were combined into two overall coping strategies: active coping and avoidant coping. Ten years later, the participants were followed for a 52-week period in a register on social benefits. Logistic regression was applied to data, with adjustment for covariates: sex, parents' socio-economic status (education and income) and self-rated health. Results: A total of 2203 (78%) participants were categorised as high LMP at follow-up. No significant associations were found between active coping in adolescence and LMP in 2014/2015. For avoidant coping, in the fully adjusted model, medium-level avoidant coping was associated with higher odds (odds ratio (OR)=1.02 (95% confidence interval (CI) 0.83–1.25) of high LMP. For low avoidant coping, the OR was 1.37 (95% 1.07–1.75). For both coping strategies, sex did not modify the association. Conclusions: Findings showed that avoidant coping was significantly associated with high LMP. Further research is needed to investigate coping in relation to specific problem areas. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is associated with an increased risk of future diabetes in both mother, father and offspring. More knowledge is needed about how to effectively reduce the risk of diabetes through sustained behavioural interventions in these families. The Face-it intervention is a complex health promotion intervention embedded in multi-level supportive environments. The aim of the intervention is to reduce type 2 diabetes risk and increase quality of life among families in the first year following a GDM-affected pregnancy by promoting physical activity, healthy dietary behaviours and breastfeeding through a focus on social support, motivation, self-efficacy, risk perception and health literacy.Methods: This national multicentre study is a two-arm randomised controlled trial including 460 women with GDM in a ratio of 2 (intervention):1 (usual care). The Face-it intervention consists of three main components: 1) additional visits from municipal health visitors, 2) digital health coaching tailored to family needs and 3) a structured cross-sectoral communication system in the health care system. The intervention runs from 3 to 12 months after delivery. The primary outcome is maternal body mass index at 12 months after delivery as a proxy for diabetes risk. The women will be examined at baseline and at follow-up, and this examination will include blood tests, oral glucose tolerance test (OGTT), anthropometrics, blood pressure, self-reported diet and physical activity, breastfeeding, quality of life, health literacy, physical and mental health status, risk perception and social support. Aside from those data collected for OGTT and breastfeeding and offspring parameters, the same data will be collected for partners. Data on offspring anthropometry will also be collected. Information on pregnancy- and birth-related outcomes will be derived from the medical records of the woman and child.Discussion: This randomised controlled trial seeks to demonstrate whether the Face-it intervention, addressing the individual, family and health care system levels, is superior to usual care in reducing diabetes risk for mothers and their families. Coupled with a process evaluation and an economic analysis, the study will provide evidence for policymakers and health services about health promotion among families affected by GDM and the potential for reducing risk of type 2 diabetes and associated conditions.Trial Registration: ClinicalTrials.gov NCT03997773. Registered June 25, 2019 - Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background and Aim: Pain is the primary symptom of chronic pancreatitis (CP) and associates with a number of patient and disease characteristics. However, the complex interrelations of these parameters are incompletely understood, and pain treatment remains unsatisfactory in a large proportion of patients. The aim of this study is to investigate multiple pain risk factors in a large population of CP patients, with a special emphasis on patients' patterns of smoking and alcohol use. Methods: This was a multicenter, cross‐sectional study including 1384 patients with CP. Patient demographics and disease characteristics, as well as current patterns of smoking and alcohol use, were compared for patients with pain (n = 801) versus without pain (n = 583). Multivariate logistic regression models were performed to assess the variables associated with the presence and type of pain (constant vs intermittent pain). Results: The mean age of participants was 52.1 ± 14.6 years, and 914 (66%) were men. Active smoking (odds ratio 1.6 [95% confidence interval 1.1–2.2], P = 0.005) and alcohol consumption (odds ratio 1.8 [95% confidence interval 1.1–3.0], P = 0.03) were independently associated with the presence of pain. In addition, patients' age at diagnosis, pancreatic duct pathology, and the presence of pseudocysts, duodenal stenosis, and exocrine pancreatic insufficiency were confirmed as pain risk factors (all P ≤ 0.01). Constant pain, as opposed to intermittent pain, was more frequently reported by smokers (P = 0.03), while alcohol consumption was associated with intermittent pain (P = 0.006). Conclusion: Multiple patient and disease characteristics, including patterns of smoking and alcohol consumption, associate with the presence and type of pain in patients with CP. [ABSTRACT FROM AUTHOR]

Failed fertilization after intracytoptasmic sperm injection (ICSI) can be due to a reduced oocyte-activation capacity caused by reduced concentrations and abnormal localization of the oocyte-activation factor phospholipase C (PLC) zeta. Patients with this condition can be helped to conceive by artificial activation of oocytes after ICSI with calcium ionophore (assisted oocyte activation; AOA). However some concern still exists about this approach. Mouse models could help to identify potential oocyte-activation strategies and evaluate their safety. In this study, the fertilizing capacity of wobbler sperm celts was tested and the efficiency of AOA with two exposures to ionomycin to restore fertilization and embryo development was studied. The quality of the obtained blastocysts was assessed and embryo transfer was performed to evaluate post-implantation development. The presence of PLCzeta in the spermatozoa and testis of the wobbler mouse was evaluated by PLCzeta immunostaining and quantitative reverse-transcription potymerase chain reaction. Sperm celts from wobbler mice had reduced fertilizing capacity and abnormalities in PLCzeta localization, but not in its expression. Artificially activating the oocytes restored fertilization and embryo development. Therefore, the wobbler mouse can be a model for failed fertilization after ICSI to study PLCzeta dynamics and aid in optimization of the AOA method. [ABSTRACT FROM AUTHOR]

Rationale: Although the antidepressant and anxiolytic effects of selective serotonin reuptake inhibitors and serotonin–noradrenaline reuptake inhibitors are well-documented, less is known about their cognitive effects. Objective: Escitalopram, a selective serotonin reuptake inhibitor, and atomoxetine, a selective noradrenaline reuptake inhibitor, were used to evaluate the interaction between noradrenergic and serotonergic neurotransmission in the modulation of contextual fear conditioning in rats. Methods: Contextual fear-conditioning test was used to investigate the acute effects of escitalopram, alone or in combination with atomoxetine, in different stages of learning and memory in rats. Furthermore, microdialysis in freely moving animals was used to investigate the effect of escitalopram on serotonin, dopamine, and noradrenaline levels in the rat hippocampus. Results: Escitalopram significantly increased conditioned responses when applied before the acquisition, but decreased responses, when applied before the recall test. When administered during memory consolidation, escitalopram dose-dependently enhanced conditioned responding. These effects were blocked by atomoxetine. Escitalopram (at a dose that affects memory consolidation) increased hippocampal serotonin levels fourfold without changing dopamine or noradrenaline. Atomoxetine, at dose levels that blocked the effects of escitalopram on contextual fear conditioning, increased the extracellular levels of noradrenaline eightfold but did not change dopamine or serotonin. A combined treatment of escitalopram and atomoxetine caused a significant attenuation of escitalopram-induced increase in serotonin levels, while noradrenaline levels were not affected. Conclusions: These findings indicate that escitalopram affects fear memory in rats, likely modulated by increases in serotonin levels in the brain. This effect is impaired by atomoxetine, probably due to a noradrenaline-mediated decrease in serotonin levels. Further studies are warranted to study the effects of potential differences among antidepressant therapies on long-term cognitive outcomes. [ABSTRACT FROM AUTHOR]