Addressing Cognitive Function and Psychological Well-Being in Chronic Kidney Disease: A Systematic Review on the Use of Technology-Based Interventions.

Patients with chronic kidney disease (CKD) are at risk of both a gradual decline in cognitive function and an increase in psychological distress. This includes symptoms of anxiety, depression, and sleep disturbances, all of which are factors that have been associated with increased morbidity and mortality. In response, we are now seeing that interventions based on new digital technologies are increasingly used in order to optimize patients' quality of life. Systematic research of the literature on electronic databases (MEDLINE/PubMed, Scopus, Web of Science, and PsycInfo/ProQuest) covering the period from 2012 to 2022 was conducted in order to methodically review the existing evidence regarding the implementation and effectiveness of technology-based interventions in the management of cognitive and psychological well-being symptoms in patients with CKD. A total of 739 articles were retrieved, 13 of which are included in the present review. All the studies focused on the usability, acceptability, and feasibility of technology-based interventions aimed at psychological symptoms, with no studies targeting cognitive functioning. Technology-based interventions offer feelings of safety, fun, and satisfaction, and they also have the potential to improve CKD patients' health outcomes regarding their psychological well-being. The diverseness of technologies allows an approximation towards the identification of those types of technologies most frequently used, as well as the symptoms targeted. There was considerable heterogeneity in the types of technologies used for interventions in so few studies, making it difficult to draw conclusive findings with regard to their efficiency. In order to adequately assess the technology-based health interventions effect, future lines of research should consider designing non-pharmacological treatments for the improvement of cognitive and psychological symptoms in this type of patient.

Factors Influencing Intention to Technological Use in Older Adults. The TAM Model Aplication.

The use of digital technology by older adults has improved in recent years in response to the need for their functional adaptation to an increasingly technological social context. Understanding this type of technological adaptation has recently become an important field of inquiry in both social and gerontological studies. Working within this framework, the aim of this study is to identify the main determinants that influence the intention of older people to use digital technology in their daily lives, using the Technological Acceptance Model. A study was carried out with the participation of 1155 people over 65 years of age in Spain. Confirmatory Factor Analysis and structural equation models (SEM) were performed. The results show that the TAM is a useful model to explain the intention of older adults to use Digital Technology, showing a high predictive power, highlighting Perceived Usefulness and Perceived Ease of Use as the main predictor variables.

Una revisión sistemática acerca del reconocimiento facial de las emociones en la Enfermedad de Alzheimer: una perspectiva evolutiva y de género / A systematic review of facial emotion recognition in Alzheimer's disease: A developmental and gender perspective

La correcta identificación de las emociones básicas (alegría, miedo, asco, tristeza, sorpresa e ira) desempeña un importante papel en las relaciones sociales y conductas ligadas a la propia supervivencia. En la Enfermedad de Alzheimer (EA) la capacidad de reconocimiento emocional podría estar ya alterada en fases iniciales. Por ello, el objetivo principal del presente trabajo fue realizar una revisión sistemática de la literatura acerca del reconocimiento emocional en personas con EA, identificando posibles variables moduladoras. Se realizó una búsqueda en las bases de datos Web of Science y PsycINFO. Después de aplicar los criterios de inclusión-exclusión se seleccionaron un total de 28 artículos. Las imágenes estáticas fueron los estímulos más utilizados para evaluar el reconocimiento de las emociones básicas, especialmente las fotografías desarrolladas por Paul Ekman y colaboradores. Los resultados de la revisión indican que las personas con EA generalmente muestran déficit del reconocimiento emocional, aunque los datos no son concluyentes. Ello podría estar relacionado con la diversidad de metodologías aplicadas. En relación con las variables evaluadas (sexo y edad) se pone de manifiesto la necesidad de futuras investigaciones que estudien de forma sistemática cómo estos factores pueden modular el reconocimiento emocional en pacientes con EA.(AU)

The correct identification of basic emotions (joy, fear, disgust, sadness, surprise and anger) plays an important role in social relationships and behaviors linked to one's survival. In Alzheimer's disease (AD), the ability to recognize emotions may already be impaired at early stages of the disease. Therefore, the main objective of the present study was to carry out a systematic review of the literature on facial emotional recognition in people with AD, identifying possible modulating variables. A search on the Web of Science and PsycInfo databases was carried out. After applying the inclusion-exclusion criteria, a total of 28 articles were selected. Static images were the most used stimuli to evaluate the recognition of basic emotions, especially the photographs developed by Paul Ekman and collaborators. Results of the present review indicate that people with AD generally display deficits in emotional recognition, although data are not conclusive, which could be related to the diversity of methodologies applied. In relation to the variables evaluated (sex and age), the need of further research in order to study how these factors could modulate emotional recognition in AD patients is highlighted.(AU)

Research on Emotion Recognition and Dementias: Foundations and Prospects.

BACKGROUND: The study of emotion recognition could be crucial for detecting alterations in certain cognitive areas or as an early sign of neurological disorders. OBJECTIVE: The main objective of the study is to characterize research development on emotion recognition, identifying the intellectual structure that supports this area of knowledge, and the main lines of research attracting investigators' interest. METHODS: We identified publications on emotion recognition and dementia included in the Web of Science Core Collection, analyzing the scientific output and main disciplines involved in generating knowledge in the area. A co-citation analysis and an analysis of the bibliographic coupling between the retrieved documents elucidated the thematic orientations of the research and the reference works that constitute the foundation for development in the field. RESULTS: A total of 345 documents, with 24,282 bibliographic references between them, were included. This is an emerging research area, attracting the interest of investigators in Neurosciences, Psychology, Clinical Neurology, and Psychiatry, among other disciplines. Four prominent topic areas were identified, linked to frontotemporal dementia, autism spectrum disorders, Alzheimer's disease, and Parkinson's and Huntington disease. Many recent papers focus on the detection of mild cognitive impairment. CONCLUSION: Impaired emotion recognition may be a key sign facilitating the diagnosis and early treatment of different neurodegenerative diseases as well as for triggering the necessary provision of social and family support, explaining the growing research interest in this area.

Behavioral impact of experience based on environmental enrichment: Influence of age and duration of exposure in male NMRI mice.

Prior studies have suggested that short periods of exposure to environmental enrichment (EE) in rodents induce physiological and behavioral effects. In the present study, our aim was to evaluate if the impact of experiences based on EE could be modulated by the age of onset and the developmental period of exposure. NMRI male mice (n = 64) were exposed to EE or standard environment (SE) and behavioral changes (anxiety, exploration, memory and social interaction) were evaluated. Groups compared were: (a) SE: exposure to SE on post-natal day (PND) 28 and lasting 6 months; (b) EE-6: exposure to EE on PND 28 and lasting 6 months; (c) EE-4: exposure to EE on PND 91 and lasting 4 months; (d) EE-2: exposure to EE on PND 154 and lasting 2 months. Results indicated that in the hole-board task the decrease in exploratory behavior reached significance when EE was initiated at adolescence whereas anxiolytic effects in the elevated plus-maze tend to diminish after a longer period of EE. No significant effects of EE on aggressive behavior or novel object recognition were obtained. Taking these results into account, further studies are needed in order to determine the possible modulating role of age and duration of exposure to enriched environments on behavior. Results obtained could explain some discrepancies reported in previous studies, providing new evidence that could contribute to the design of future research related to the benefits of complex and enriched environments.

The Mediational Role of Burden and Perceived Stress in Subjective Memory Complaints in Informal Cancer Caregivers.

The role of informal caregiver of cancer patients is considered a situation of chronic stress that could have impact on cognitive functioning. Our aim was to evaluate differences in perceived stress, subjective memory complaints, self-esteem, and resilience between caregivers and non-caregivers, as well as the possible mediational role of burden in caregivers. The sample was composed of 60 participants divided into two groups: (1) Primary informal caregivers of a relative with cancer (CCG) (n = 34); and (2) non-caregiver control subjects (Non-CG) (n = 26). All participants were evaluated through a battery of tests: Socio-demographic questionnaire, subjective memory complaints questionnaire (MFE-30), Rosenberg Self-Esteem Scale, resilience (CD-RISC-10), and perceived stress scale (PSS). The CCG group also completed the Zarit burden interview. Results indicated that CCG displayed higher scores than Non-CG in MFE-30 (p = 0.000) and PSS (p = 0.005). In the CCG group, Pearson correlations indicated that PSS showed a negative relationship with resilience (p = 0.000) and self-esteem (p = 0.002) and positive correlation with caregiver's burden (p = 0.015). In conclusion, CCG displayed higher number of subjective memory complaints and higher perceived stress than Non-CG, whereas no significant differences were obtained on self-esteem and resilience. These results could aid in designing new intervention strategies aimed to diminish stress, burden, or cognitive effects in informal caregivers of cancer patients.

Physical activity and environmental enrichment: Behavioural effects of exposure to different housing conditions in mice.

Enriched environments and exercise provide complex environmental stimulation that can induce emotional and cognitive changes; however, few studies have evaluated the effects of these two components on other behaviours, such as novelty seeking or pain sensitivity. The aim of the present study was to investigate the influence of voluntary physical activity provided through different housing conditions on anxiety, locomotor activity, pain sensitivity, and exploration. Male mice at postnatal day (PND) 21 and were randomly assigned to one of four different conditions on PND 28: Marlau cages (MC), a standardized cage designed to provide a complex environment; physical exercise in large groups (PE­8); physical exercise in small groups (PE­4); or a standard environment (SE). After seven weeks, animals were evaluated in the hole­board task, the elevated zero maze, actimeter, and hot plate test. In the hole­board task, MC animals displayed more exploration than animals in the PE­8 and PE­4 groups, but no significant differences were observed between groups in the actimeter. In the elevated zero maze, MC and PE­8 animals exhibited an anxiogenic­like profile as compared to the SE group. When pain sensitivity was evaluated, the PE­8 group displayed a higher sensitivity to noxious thermal stimuli than the SE group. These data suggest that the complexity of the environment in which physical activity and environmental stimulation are provided can influence animal behaviours such as novelty seeking, emotional response, and pain sensitivity. These animal models could be useful for designing more personalized interventions that include physical, social, and cognitive stimulation to promote a more active lifestyle in humans. Such interventions could be useful in the prevention and treatment of aging­related decline or neurodegenerative diseases.

Methods for Evaluating the Interaction Between Social Stress and Environmental Enrichment in Animal Models of Nicotine Addiction.

The environmental enrichment (EE) paradigm has been evaluated as a means of counteracting some of the consequences of chronic stress in rodents as well as a model of protective environment against drug abuse development. In the present chapter, our main aim is to describe the models of EE and chronic social stress and how they can be applied jointly in order to evaluate the effects of early psychosocial stress in animals exposed of different environments (enriched environment or standard environment). Furthermore, both paradigms could be applied in animal models of nicotine addiction, so the guidelines for the application of a chronic oral nicotine treatment in mice will be described. The heterogeneity of the procedures carried out in different laboratories makes it interesting to specify their characteristics in order to obtain replicable and valid animal models.

An Animal Model of Alcohol Binge Drinking: Chronic-Intermittent Ethanol Administration in Rodents.

Binge drinking (BD), characterized by intermittent consumption of large quantities of alcohol in short periods of time, is the main alcohol consumption pattern in adolescents and young adults. BD has serious biomedical consequences, and it is a prominent risk factor for later development of alcohol use disorders. Rodent models offer exceptional power to study these negative consequences of BD. This chapter focuses on one of these BD models: the chronic-intermittent ethanol administration (CIEA) paradigm. Essentially, CIEA consists of the administration in rats or mice of i.p. injections of ethanol (doses: 3-4 g/kg) for several consecutive days each week, in alternation with several days without injections, during several weeks. Due to our interest in the neurobehavioral effects of BD, a combination of the CIEA model with a battery of behavioral tests is described, with emphasis on the effects of alcohol BD on different kinds of memory. The CIEA model, in combination with behavioral tasks, seems to be a useful tool for studying the neurobehavioral effects of BD as well as for developing potential prevention and treatment strategies.

Bupropion induces social anxiety in adolescent mice: Influence of housing conditions.

BACKGROUND: The antidepressant bupropion has received increasing attention as a pharmacological tool to treat addiction although little is known about its effects on social behaviour in adolescents. The present study aimed to evaluate if environmental housing conditions influence bupropion's actions on social behaviour of adolescent mice. METHODS: Mice were either group- or individually housed for 2-weeks and then randomly divided into 2 cohorts: half of the mice remained in the initial housing condition and the other half were changed to isolated conditions for further 2-weeks. The following groups were compared: isolated/isolated (ISO/ISO), isolated/group-housed (ISO/GR), group-housed/isolated (GR/ISO), and group-housed/group-housed (GR/GR). The effects of bupropion (40, 20, 10mg/kg) or saline on social interaction were assessed for each housing condition. Social encounters were evaluated using ethological analysis. RESULTS: Data showed significant effects of bupropion on grooming and digging. This drug diminished time mice allocated to these behavioural categories in all housing conditions. In ISO/GR and GR/ISO conditions, bupropion increased environmental exploration (non-social exploration and exploration from a distance), reduced social investigation and increased avoidance/flee and defence/submission behaviours. An augment of avoidance/flee during social interactions was observed in bupropion-treated mice in GR/GR housing condition. CONCLUSION: These results suggest that this drug exhibits anxiogenic-like properties in social encounters between adolescent mice, especially when a transition in housing conditions has been experienced during this period. Changes in housing conditions may be a useful model for evaluating the effects of bupropion on social behaviour and the role of environmental housing conditions.

Cuidado de pacientes oncológicos: una revisión sobre el impacto de la situación de estrés crónico y su relación con la personalidad del cuidador y otras variables moduladoras / Care of oncological patients: a review on the impact of the chronic stress situation and its relation to the caregiver personality and other modulator variables

Objetivo: La incidencia y prevalencia de enfermedades de larga duración como el cáncer se ha incrementado en los últimos años. En este contexto, nuestro principal objetivo será el análisis de las principales consecuencias que la exposición a una situación de estrés crónico, como es el cuidado de un paciente oncológico, tiene sobre la salud psicosocial y la función cognitiva del cuidador informal y su relación con variables moduladoras. Método: Se realizó una revisión bibliográfica en las bases de datos PubMed y PsychINFO sobre las consecuencias de la situación de cuidado en pacientes crónicos. Resultados: Diversos estudios sugieren que la condición de cuidador de un paciente oncológico puede considerarse una situación estresante que conlleva consecuencias tanto a nivel de salud física como psicosocial del cuidador además de un deterioro en su funcionamiento cognitivo que pueden estar modulados por diferentes variables. Conclusión: Estos datos sugieren la importancia de implementar programas de intervención que amortigüen las consecuencias deletéreas de la labor de cuidado (AU)

Objective: The prevalence of long-term diseases such as cancer has increased in recent years. In this context, our aim will be to analyze the main consequences resulting from exposure to a chronic stress situation, such as the care of an oncologic patient. The effects of this situation on the psychosocial health and cognitive function of informal caregivers and their relationship with possible modulating variables will be revised. Method: A bibliographic review was performed in PubMed and PsycINFO databases about the consequences related to the caregiving of patients with chronic diseases. Results: Several studies suggest that the condition of caregiver of cancer patients could be considered as an and stressful situation. It has consequences on caregiver’s physical and psychosocial health, and can induce a decrease of cognitive functioning, although these changes may be modulated by different variables. Conclusion: These data suggest the need of implementing intervention programs in order to mitigate the deleterious consequences of the caregiving situation (AU)

Adolescent and adult mice display differential sensitivity to the effects of bupropion on the acquisition of a water maze task.

BACKGROUND: Adolescence is characterized by major neurobiological changes, and the effects of some psychoactive drugs seem to differ between adolescents and adults. Bupropion, an antidepressant that is also used to treat nicotine addiction, induces behavioral actions in both adolescent and adult rodents. However, the effects of this drug on spatial ability have not been compared in animals at different stages of their development. The present study was conducted to assess the effects of bupropion on spatial learning and memory in adolescent and adult mice. METHODS: Adolescent (post-natal day: PND35-36) and adult (PND >65) NMRI mice received bupropion (10, 20 and 40mg/kg) or saline during the acquisition (4 trials/day on 5 consecutive days) of a Morris water maze (MWM) task. Retention was evaluated with a probe trial performed after the acquisition phase. RESULTS: Data showed that age did not affect performance of the task. However, the factor Drug treatment reached statistical significance, with high doses of bupropion (40 and 20mg/kg) impairing acquisition of the MWM test in adolescents. The drug did not induce detrimental effects on the acquisition or retention of the task in adults. CONCLUSION: Bupropion impairs acquisition of the spatial task in adolescent but not in adult mice. It does not seem to alter retrieval of previously acquired spatial information in either adolescents or adults. Our findings suggest that, during the adolescent period, mice are more vulnerable to the actions of bupropion on spatial learning.

Corticosterone levels and behavioral changes induced by simultaneous exposure to chronic social stress and enriched environments in NMRI male mice.

Environmental enrichment (EE) is an experimental model which is believed to counteract some of the effects induced by stressors, although few studies have exposed rodents simultaneously to EE and stress. Our aim was to compare the short- and long-term effects of different housing conditions in mice submitted to chronic stress. 128 NMRI male mice arrived at our laboratory on postnatal day (PND) 21. During Phase I (PND 28), animals were randomly assigned to four experimental conditions: 1) EE+STRESS: mice housed in EE and submitted to social stress (n=32); 2) EE+NO STRESS: mice housed in EE without stress (n=32); 3) SE+STRESS: mice maintained in standard conditions (SE) and submitted to social stress (n=32); and 4) SE+NO STRESS (n=32). At the end of Phase I (PND 77), one cohort of 32 animals was used for behavioral assessment whereas another cohort of 32 was sacrificed for corticosterone analysis. Results indicated that EE animals showed less body weight, higher water and food intake, diminished anxiety response and decreased motor and exploratory behavior than SE mice. Mice exposed to stress gained less body weight, showed higher food and fluid intake and displayed decreased exploratory behavior than non-stressed mice. Furthermore, EE+STRESS group displayed significantly higher corticosterone levels than EE+NO STRESS group whereas EE+NO STRESS group showed lower levels than SE+NO STRESS. On PND 83, Phase II of the study began. Animals (n=96) were assigned to two different housing conditions: EE (n=48) and SE (n=48). On PND 112, corticosterone analysis (n=32) and behavioral study (n=64) were done. The factor "Housing Phase II" reached statistical significance. Results indicated that EE animals showed lower body weight and higher fluid intake than SE group, as well as decreased anxiety. No clear effects on motor and exploratory behavior or learning were observed. When long-term effects were analyzed, results indicated that "Initial Housing" condition was significant: animals allocated in EE during Phase I of the study showed higher corticosterone levels, lower body weight and higher fluid intake than SE mice. "Initial Stress" had significant long-term actions on food intake and exploratory behavior: animals initially reared under stress conditions displayed higher food intake and lower exploration levels on the hole-board test than non-stressed mice. In the elevated plus-maze, there were significant interactions between factors "Initial Housing" and "Initial Stress". These factors did not reach statistical significance for motor activity or learning task. We can conclude that both short- and long-term effects of housing conditions are evident for corticosterone levels, body weight and fluid intake. Social stress induced short-term effects on body weight, food and fluid intake and exploratory behavior whereas long-acting effects were reflected on food intake and exploratory behavior. Further studies are needed in order to explore more in depth behavioral and physiological consequences of social stress and environmental enrichment.

Behavioral effects of different enriched environments in mice treated with the cholinergic agonist PNU-282987.

Environmental enrichment is an experimental model in which rodents are housed in complex environments that favor lower levels of anxiety-like behavior. PNU-282987 (PNU) is a α7 nicotinic acetylcholine receptor agonist with beneficial effects on learning though its effects on anxiety are unclear. Our main aim was to carry out a study of its effects in NMRI (n=96) mice reared in different environments: environmental enrichment (EE), Marlau™ cages (MC) and standard environment (SE). After a 4-month period, mice received acute treatment of PNU (2.5, 5 and 10mg/kg) and were evaluated in the elevated plus-maze (EPM) and hole-board (HB). In the EPM, both EE and MC reared mice showed an increase in percentage of entries into open arms while those from EE group differed from SE in time spent on open arms. Mice treated with 2.5 and 10 mg/kg of PNU devoted less time to rearing into open arms. In the HB task, MC mice displayed higher exploratory activity reflected in more head-dips (HD) during the first minute than EE and SE, whereas EE displayed low exploration levels reflected in total HD (5 min). Further research is needed in order to clarify the behavioral effects of this nicotinic agonist in interaction with different environmental conditions. This article is part of a Special Issue entitled: insert SI title.

Bupropion induced changes in exploratory and anxiety-like behaviour in NMRI male mice depends on the age.

The aim of this study was to assess the effects of the antidepressant bupropion on anxiety and novelty-seeking in adolescent mice of different ages and adults. Behavioural differences between early adolescent, late adolescent and adult NMRI mice were measured both in the elevated plus-maze and the hole-board tasks following acute administration of bupropion (5, 10, 15, 20mg/kg) or saline. In the plus maze test, early and late adolescent mice treated with bupropion (10, 15mg/kg, respectively) had lower percentages of entries in the open-arms compared to their vehicle controls. Adult mice treated with bupropion did not differ from their vehicle controls. These results suggest that the effect of this drug on anxiety-like behaviour in mice depends on the age, showing adolescents an anxiogenic-like profile. In the hole-board, adolescents showed more elevated levels of novelty-seeking than adults, exhibiting shorter latency to the first head-dip (HD) and a higher number of HD's. Bupropion increases the latency to the first HD and decreases the number of HD's in all age-groups, indicating a decline in exploratory tendency. Findings reveal that the age can modulate the behaviour displayed by mice in both animal models, and that adolescents are more sensitive to bupropion's anxiogenic effects.

Environmental enrichment improves novel object recognition and enhances agonistic behavior in male mice.

Environmental enrichment (EE) is an experimental paradigm in which rodents are housed in complex environments containing objects that provide stimulation, the effects of which are expected to improve the welfare of these subjects. EE has been shown to considerably improve learning and memory in rodents. However, knowledge about the effects of EE on social interaction is generally limited and rather controversial. Thus, our aim was to evaluate both novel object recognition and agonistic behavior in NMRI mice receiving EE, hypothesizing enhanced cognition and slightly enhanced agonistic interaction upon EE rearing. During a 4-week period half the mice (n = 16) were exposed to EE and the other half (n = 16) remained in a standard environment (SE). On PND 56-57, animals performed the object recognition test, in which recognition memory was measured using a discrimination index. The social interaction test consisted of an encounter between an experimental animal and a standard opponent. Results indicated that EE mice explored the new object for longer periods than SE animals (P < .05). During social encounters, EE mice devoted more time to sociability and agonistic behavior (P < .05) than their non-EE counterparts. In conclusion, EE has been shown to improve object recognition and increase agonistic behavior in adolescent/early adulthood mice. In the future we intend to extend this study on a longitudinal basis in order to assess in more depth the effect of EE and the consistency of the above-mentioned observations in NMRI mice.

Behavioral effects of combined environmental enrichment and chronic nicotine administration in male NMRI mice.

Environmental enrichment (EE) is an experimental paradigm which provides sensory, social, physical and cognitive stimulation for rodents. Experimental evidence indicates that this type of housing induces different neurobiological and behavioral changes. However, few studies have evaluated the consequences of combined exposure to an enriched environment and nicotine administration during a critical period of development such as adolescence. Taking into account previous studies, it can be hypothesized that a chronic treatment with nicotine would modulate the effects of rearing animals in enriched environments. In the current study, our main aim was to evaluate the effects of EE and chronic nicotine administration on physiological parameters (weight, fluid intake and cotinine levels), motor activity, exploratory behavior, anxiety and learning in male NMRI mice. Half of the mice (n=32) were exposed to an enriched environment (EE) and the other half (n=32) were housed in standard environments (SE) with or without oral nicotine administration (100 µg/ml). After 3 weeks, mice were evaluated in a behavioral battery that included an elevated plus-maze, a hole board, an actimeter and an inhibitory avoidance task. Blood cotinine levels were measured in an additional group of 32 mice in order to confirm nicotine intake. Results indicated that mice reared in an enriched environment gained less body weight and displayed higher fluid intake than those maintained in a standard environment. EE reduced motor activity, exploratory behavior and anxiety, whereas it enhanced inhibitory avoidance learning. In relation to the effects of chronic nicotine treatment, the data reflected a lower increase in body weight and a reduced fluid intake in nicotine-treated mice. In the elevated plus-maze, nicotine induced a reduction of total arm entries and rearings. Cotinine levels were higher in mice that received oral nicotine than in the control group. We conclude that the EE paradigm applied in this study induces physiological and behavioral changes in NMRI mice. Chronic nicotine treatment diminished motor activity displayed by mice in the elevated plus-maze but did not have significant effects on inhibitory avoidance learning. Future studies should explore in greater depth the interaction between environmental factors and nicotine administration using longer periods of EE, a wider range of doses and/or other cholinergic agonists, acute drug administration, and sequential exposure to nicotine and EE.

Enriched environments for rodents and their interaction with nicotine administration.

An active lifestyle throughout the life cycle seems to delay cognitive aging and dementia and has also been evaluated as an intervention against addiction to cocaine and other drugs of abuse. In epidemiological studies with humans, it has proved difficult to separate the cognitive, social and physical components from other variables that influence lifestyle. Studies in animal models are useful for evaluating the impact of each of these factors and for uncovering the underlying mechanisms of the benefits of complex environments. Preclinical studies have employed the Environmental Enrichment paradigm (EE) which has been proposed as a preclinical model of positive life experiences in humans. EE has been associated with protective effects against addiction to some drugs, but few studies have been carried out in order to evaluate how its actions interact with nicotine addiction. In this context, the main aim of this review is to provide an analysis of the preclinical studies evaluating the interaction between exposure to enriched environments with the neurobiological and behavioral effects of nicotine administration. These studies will contribute to the development of future preventive and therapeutic applications of enriched environments and positive experiences for drug addiction in human beings, taking into account individual vulnerability. They also may shed light on new approaches to the treatment of nicotine addiction, as interventions based in physical exercise in interaction with other environmental variables.

Potential benefits and limitations of enriched environments and cognitive activity on age-related behavioural decline.

The main aim of this chapter is to review preclinical studies that have evaluated interventions which may aid in preventing or delaying age-related behavioural decline. Animal models of Environmental Enrichment (EE) are useful for evaluating the influence of cognitive, physical and social stimulation in mitigating cognitive decline at different ages. The EE paradigm has been proposed as a non-invasive treatment for alleviating age-related memory impairment and neurodegenerative diseases. While in this complex environment, rodents can be stimulated at different levels (physical, social, cognitive and sensorial), although a synergism between all these components is likely to play an important role. We will summarize available data relating to EE as a potential therapeutic strategy that slows down or counteracts age-related cognitive and behavioural changes. EE also alters physiological responses and induces neurobiological changes such as stimulation of neurogenesis and neural plasticity. At the behavioural level, EE improves learning and memory tasks and reduces anxiety. Several variables seem to influence the behavioural and cognitive benefits induced by EE, including the age at which animals are first exposed to EE, total period during which animals are submitted to EE, gender, the cognitive task evaluated, the drug administered and individual factors. Cognitive and physical stimulation of animals in enriched experimental environments may lead to a better understanding of factors that promote the formation of cognitive reserve (CR) and a healthier life in humans. In the present chapter we review the potential benefits of EE in aged rodents and in animal models of Alzheimer Disease (AD). Results obtained in preclinical models of EE may be relevant to future research into mental and neurodegenerative diseases, stress, aging and development of enviromimetics. Finally, we outline the main limitations of EE studies (variability between laboratories, difficulty of separating the different components of EE, gender of experimental subjects, individual differences in the response to EE), evaluating the potential benefits of enriched environments and the neurobiological mechanisms that underlie them. We conclude that there are experimental data which demonstrate the cognitive benefits of rearing rodents in enriched environments and discuss their implication for clarifying which variables contribute to the formation of the CR.