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BACKGROUND: With the rapid aging of the global population, the prevalence of mild cognitive impairment (MCI) and dementia is anticipated to surge worldwide. MCI serves as an intermediary stage between normal aging and dementia, necessitating more sensitive and effective screening tools for early identification and intervention. The BrainFx SCREEN is a novel digital tool designed to assess cognitive impairment. This study evaluated its efficacy as a screening tool for MCI in primary care settings, particularly in the context of an aging population and the growing integration of digital health solutions. OBJECTIVE: The primary objective was to assess the validity, reliability, and applicability of the BrainFx SCREEN (hereafter, the SCREEN) for MCI screening in a primary care context. We conducted an exploratory study comparing the SCREEN with an established screening tool, the Quick Mild Cognitive Impairment (Qmci) screen. METHODS: A concurrent mixed methods, prospective study using a quasi-experimental design was conducted with 147 participants from 5 primary care Family Health Teams (FHTs; characterized by multidisciplinary practice and capitated funding) across southwestern Ontario, Canada. Participants included health care practitioners, patients, and FHT administrative executives. Individuals aged ≥55 years with no history of MCI or diagnosis of dementia rostered in a participating FHT were eligible to participate. Participants were screened using both the SCREEN and Qmci. The study also incorporated the Geriatric Anxiety Scale-10 to assess general anxiety levels at each cognitive screening. The SCREEN's scoring was compared against that of the Qmci and the clinical judgment of health care professionals. Statistical analyses included sensitivity, specificity, internal consistency, and test-retest reliability assessments. RESULTS: The study found that the SCREEN's longer administration time and complex scoring algorithm, which is proprietary and unavailable for independent analysis, presented challenges. Its internal consistency, indicated by a Cronbach α of 0.63, was below the acceptable threshold. The test-retest reliability also showed limitations, with moderate intraclass correlation coefficient (0.54) and inadequate κ (0.15) values. Sensitivity and specificity were consistent (63.25% and 74.07%, respectively) between cross-tabulation and discrepant analysis. In addition, the study faced limitations due to its demographic skew (96/147, 65.3% female, well-educated participants), the absence of a comprehensive gold standard for MCI diagnosis, and financial constraints limiting the inclusion of confirmatory neuropsychological testing. CONCLUSIONS: The SCREEN, in its current form, does not meet the necessary criteria for an optimal MCI screening tool in primary care settings, primarily due to its longer administration time and lower reliability. As the number of digital health technologies increases and evolves, further testing and refinement of tools such as the SCREEN are essential to ensure their efficacy and reliability in real-world clinical settings. This study advocates for continued research in this rapidly advancing field to better serve the aging population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/25520.
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Disfunção Cognitiva , Demência , Humanos , Feminino , Idoso , Masculino , Demência/psicologia , Psicometria , Reprodutibilidade dos Testes , Estudos Prospectivos , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Sensibilidade e Especificidade , OntárioRESUMO
BACKGROUND: The integration of smart technologies, including wearables and voice-activated devices, is increasingly recognized for enhancing the independence and well-being of older adults. However, the long-term dynamics of their use and the coadaptation process with older adults remain poorly understood. This scoping review explores how interactions between older adults and smart technologies evolve over time to improve both user experience and technology utility. OBJECTIVE: This review synthesizes existing research on the coadaptation between older adults and smart technologies, focusing on longitudinal changes in use patterns, the effectiveness of technological adaptations, and the implications for future technology development and deployment to improve user experiences. METHODS: Following the Joanna Briggs Institute Reviewer's Manual and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines, this scoping review examined peer-reviewed papers from databases including Ovid MEDLINE, Ovid Embase, PEDro, Ovid PsycINFO, and EBSCO CINAHL from the year 2000 to August 28, 2023, and included forward and backward searches. The search was updated on March 1, 2024. Empirical studies were included if they involved (1) individuals aged 55 years or older living independently and (2) focused on interactions and adaptations between older adults and wearables and voice-activated virtual assistants in interventions for a minimum period of 8 weeks. Data extraction was informed by the selection and optimization with compensation framework and the sex- and gender-based analysis plus theoretical framework and used a directed content analysis approach. RESULTS: The search yielded 16,143 papers. Following title and abstract screening and a full-text review, 5 papers met the inclusion criteria. Study populations were mostly female participants and aged 73-83 years from the United States and engaged with voice-activated virtual assistants accessed through smart speakers and wearables. Users frequently used simple commands related to music and weather, integrating devices into daily routines. However, communication barriers often led to frustration due to devices' inability to recognize cues or provide personalized responses. The findings suggest that while older adults can integrate smart technologies into their lives, a lack of customization and user-friendly interfaces hinder long-term adoption and satisfaction. The studies highlight the need for technology to be further developed so they can better meet this demographic's evolving needs and call for research addressing small sample sizes and limited diversity. CONCLUSIONS: Our findings highlight a critical need for continued research into the dynamic and reciprocal relationship between smart technologies and older adults over time. Future studies should focus on more diverse populations and extend monitoring periods to provide deeper insights into the coadaptation process. Insights gained from this review are vital for informing the development of more intuitive, user-centric smart technology solutions to better support the aging population in maintaining independence and enhancing their quality of life. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/51129.
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Dispositivos Eletrônicos Vestíveis , Humanos , Idoso , Pessoa de Meia-Idade , Feminino , Masculino , Idoso de 80 Anos ou mais , Voz , Estudos LongitudinaisRESUMO
BACKGROUND: People working in long-term care homes (LTCH) face difficult decisions balancing the risk of infection spread with the hardship imposed on residents by infection control and prevention (ICP) measures. The Dementia Isolation Toolkit (DIT) was developed to address the gap in ethical guidance on how to safely and effectively isolate people living with dementia while supporting their personhood. In this observational study, we report the results of a survey of LTCH staff on barriers and facilitators regarding isolating residents, and the impact of the DIT on staff moral distress. METHODS: We completed an online cross-sectional survey. Participants (n = 207) were staff working on-site in LTCH in Ontario, Canada since March 1, 2020, with direct or indirect experience with the isolation of residents. LTCH staff were recruited through provincial LTCH organizations, social media, and the DIT website. Survey results were summarized, and three groups compared, those: (1) unfamiliar with, (2) familiar with, and (3) users of the DIT. RESULTS: 61% of respondents identified distress of LTCH staff about the harmful effects of isolation on residents as a major barrier to effective isolation. Facilitators for isolation included delivery of 1:1 activity in the resident's room (81%) and designating essential caregivers to provide support (67%). Almost all respondents (84%) reported an increase in moral distress. DIT users were less likely to report an impact of moral distress on job satisfaction (odds ratio (OR) 0.41, 95% CI 0.19-0.87) with 48% of users reporting the DIT was helpful in reducing their level of moral distress. CONCLUSIONS: Isolation as an ICP measure in LTCH environments creates moral distress among staff which is a barrier to its effectiveness. ICP guidance to LTCH would be strengthened by the inclusion of a dementia-specific ethical framework that addresses how to minimize the harms of isolation on both residents and staff.
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Demência , Assistência de Longa Duração , Estudos Transversais , Demência/diagnóstico , Demência/epidemiologia , Demência/prevenção & controle , Humanos , Ontário/epidemiologia , Inquéritos e QuestionáriosRESUMO
The increasing complexity of residents' needs, emphasis on social distancing and limited access to high-quality support presented challenges to patient-centred care during the pandemic. Yet the pandemic created an opportunity to explore novel approaches to achieving person-centred care within long-term care (LTC). We share three projects designed to enhance care delivery in the context of the pandemic: to address personhood needs during outbreaks, to improve the quality of medical care and to deliver personalized palliative and end-of-life care using a prediction algorithm. These projects enabled better care during the pandemic and will continue to advance person-centred care beyond the pandemic.
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COVID-19 , Assistência Terminal , Humanos , Idoso , Assistência de Longa Duração , Pandemias , COVID-19/epidemiologia , Assistência Centrada no PacienteRESUMO
The COVID-19 pandemic rattled Canada's long-term care (LTC) sector by exacerbating the ingrained systemic and structural issues, resulting in tragic consequences for the residents, family members and LTC staff. At the core of LTC's challenges is chronic under-staffing, leading to lower quality of care for residents and higher degrees of moral distress among staff. A rejuvenation of the LTC sector to support its workforce is overdue. A group of diverse and renowned researchers from across Canada set out to implement innovative evidence-informed solutions in various LTC homes. Their findings call for immediate action from policy makers and LTC decision makers.
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COVID-19 , Assistência de Longa Duração , Humanos , COVID-19/epidemiologia , Canadá/epidemiologia , Pandemias , Recursos HumanosRESUMO
Several lines of evidence suggest that there may be a shared vulnerability to acquire behaviors motivated by strong incentive stimuli. Non-food restricted male Sprague-Dawley rats (n = 78) underwent place conditioning with Oreos, and were subsequently tested on cocaine self-administration (SA) on fixed and progressive ratios, as well as extinction and reinstatement by cocaine primes and by consumption of Oreos. Although there was a group preference for the Oreo-paired compartment, at the individual level some rats (69%) displayed a preference and others did not. In cocaine SA, 'preference' rats achieved higher break points on a progressive ratio, and displayed greater responding during extinction and cocaine-induced reinstatement. Within the context of this study, Oreo-cocaine cross-reinstatement was not observed. In a control study, rats (n = 29) conditioned with a less palatable food (rice cakes) also displayed individual differences in place preference, but not on subsequent cocaine tests. These findings indicate that there is a relationship between incentive learning promoted by palatable foods and by cocaine. This supports the hypothesis that co-morbid food-drug addictions may result from a shared vulnerability to acquire behaviors motivated by strong incentives.
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Comportamento Aditivo/psicologia , Cocaína/farmacologia , Suscetibilidade a Doenças , Inibidores da Captação de Dopamina/farmacologia , Comportamento de Procura de Droga/fisiologia , Motivação , Análise de Variância , Animais , Comportamento de Escolha/fisiologia , Cocaína/administração & dosagem , Condicionamento Operante/fisiologia , Inibidores da Captação de Dopamina/administração & dosagem , Extinção Psicológica/fisiologia , Preferências Alimentares/fisiologia , Humanos , Infusões Intravenosas , Masculino , Ratos , Ratos Sprague-Dawley , Esquema de Reforço , Autoadministração/estatística & dados numéricos , Fatores de TempoRESUMO
BACKGROUND: The Internet of Things (IoT) has gained significant attention due to advancements in technology and has potential applications in meeting the needs of an aging population. Smart technologies, a subset of IoT, can support older adults in aging in place, promoting independent living and improving their quality of life. However, there is a lack of research on how older adults and smart technologies coadapt over time to maximize their benefits and sustain adoption. OBJECTIVE: We will aim to comprehensively review and analyze the existing scientific literature pertaining to the coadaptation between smart technologies and older adults. The primary focus will be to investigate the extent and nature of this coadaptation process and explore how older adults and technology coevolve over time to enhance older adults' experience with technology. METHODS: This scoping review will follow the methodology outlined in the Joanna Briggs Institute Reviewer's Manual and adhere to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews) guidelines for reporting. Peer-reviewed articles will be searched in databases like Ovid MEDLINE, OVID Embase, PEDro, OVID PsycINFO, EBSCO CINAHL, the Cochrane Library, Scopus, IEEE Xplore, Web of Science, and Global Index Medicus. The research team will create a data extraction form covering study characteristics, participant characteristics, underlying models and frameworks, research findings, implications for technology coadaptation, and any identified study limitations. A directed content analysis approach will be used, incorporating the Selection, Optimization, and Compensation framework and Sex- and Gender-Based Analysis Plus theoretical framework. RESULTS: The results of this study are expected in January 2024. CONCLUSIONS: This scoping review endeavors to present a thorough overview of the available evidence concerning how smart technologies interact with older adults over an extended period. The insights gained from this review will lay the groundwork for a research program that explores how older adults adapt to and use smart technologies throughout their lives, ultimately leading to improved user satisfaction and experience and facilitating aging in place with tailored support and user-centered design principles. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/51129.
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Healthcare providers caring for people living with dementia may experience moral distress when faced with ethically challenging situations, such as the inability to provide care that is consistent with their values. The COVID-19 pandemic produced conditions in long-term care homes (hereafter referred to as 'care homes') that could potentially contribute to moral distress. We conducted an online survey to examine changes in moral distress during the pandemic, its contributing factors and correlates, and its impact on the well-being of care home staff. Survey participants (n = 227) working in care homes across Ontario, Canada were recruited through provincial care home organizations. Using a Bayesian approach, we examined the association between moral distress and staff demographics and roles, and characteristics of the long-term care home. We performed a qualitative analysis of the survey's free-text responses. More than 80% of care home healthcare providers working with people with dementia reported an increase in moral distress since the start of the pandemic. There was no difference in the severity of distress by age, sex, role, or years of experience. The most common factors associated with moral distress were lack of activities and family visits, insufficient staffing and high turnover, and having to follow policies and procedures that were perceived to harm residents with dementia. At least two-thirds of respondents reported feelings of physical exhaustion, sadness/anxiety, frustration, powerlessness, and guilt due to the moral distress experienced during the pandemic. Respondents working in not-for-profit or municipal homes reported less sadness/anxiety and feelings of not wanting to go to work than those in for-profit homes. Front-line staff were more likely to report not wanting to work than those in management or administrative positions. Overall, we found that increases in moral distress during the pandemic negatively affected the well-being of healthcare providers in care homes, with preliminary evidence suggesting that individual and systemic factors may intensify the negative effect.
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COVID-19 , Demência , Humanos , Pandemias , Assistência de Longa Duração , Estresse Psicológico , Prevalência , Teorema de Bayes , Pessoal de Saúde , Princípios Morais , OntárioRESUMO
The aim of this study was to explore the psychopharmacological characteristics of opioid-induced conditioned reinforcement using oxycodone, a potent mu-opioid receptor agonist with known abuse potential. In differed groups of rats, passive intravenous infusions of oxycodone (100 infusions/3 h×6 sessions in total; 0, 0.01, 0.05 and 0.1 mg/kg/inf) were paired with an audio-visual stimulus and, subsequently, operant responding maintained by this conditioned stimulus was tested in extinction conditions. It was found that the oxycodone-paired stimulus maintained operant responding and that this effect was dependent on the number of conditioning sessions and on the conditioning dose. Responding maintained the oxycodone-paired stimulus could also be reinstated by both foot-shock stress and by oxycodone priming (0.25 mg/kg, SC). A conditioned place preference experiment (3 drug and 3 vehicle injections over 6 days; oxycodone: 0, 0.25, 2 and 5 mg/kg, SC) confirmed that stimuli associated with lower doses of oxycodone induce conditioned approach. Finally, two control experiments performed with chlordiazepoxide ruled out an interpretation of the oxycodone data based on drug-induced amnesia, and confirmed that operant responding for a drug-conditioned stimulus is observed only when the drug possesses unconditioned reinforcing properties. Therefore, the intravenous conditioned reinforcement procedure appears a useful method to study how opioid drugs impart reinforcing value to discrete environmental stimuli.
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Condicionamento Operante/efeitos dos fármacos , Entorpecentes/administração & dosagem , Oxicodona/administração & dosagem , Reforço Psicológico , Animais , Masculino , Entorpecentes/farmacologia , Oxicodona/farmacologia , Psicofarmacologia/métodos , Ratos , Ratos Sprague-Dawley , Esquema de ReforçoRESUMO
BACKGROUND: With the rapid aging of the global population, experts anticipate a surge in the prevalence of mild cognitive impairment (MCI) and dementia worldwide. It is argued that developing more sensitive, easy to administer, and valid MCI screening tools for use in primary care settings may initiate timely clinical and personal care planning and treatment, enabling early access to programs and services. Including functional competence measures in screening tests makes them more ecologically valid and may help to identify cognitive deficits at an earlier stage. OBJECTIVE: We aim to conduct a preliminary evaluative study comparing the sensitivity, specificity, and reliability of the BrainFx Screen (referred to as SCREEN hereafter), a novel digital tool designed to assess functional competence and detect early signs of cognitive impairment, with the Quick Mild Cognitive Impairment, a validated and highly sensitive tool that detects MCI in the older adult population. We will also investigate the perceived usefulness and integration of the SCREEN into primary care practice to identify demonstrable impacts on clinical workflow and health care providers' (HCP) perceptions of its success as a screening tool. Patients' perceptions of completing the SCREEN and its impact on their quality of life will also be explored. METHODS: This study has a concurrent, mixed methods, prospective, and quasi-experimental design. Participants will be recruited from 5 primary care family health teams (FHTs; defined by multidisciplinary practice and capitated funding) across southwestern Ontario, Canada. Participants will include HCPs, patients, care partners, and FHT administrative executives. Patients 55 years and older with no history of diagnoses for MCI, dementia, or Alzheimer disease rostered in one of the FHTs participating in the study will be eligible to participate. Their care partners will help triangulate the qualitative data collected from patients. Participating FHTs will identify an occupational therapist from their site to participate in the study; this HCP will both administer the research protocol and participate in semistructured in-depth interviews and questionnaires. Principal component analysis will be conducted on the SCREEN data to understand the test components better. Tests comparing sensitivity, specificity, and test-retest reliability will assess the validity of SCREEN as a screening tool for MCI. RESULTS: This paper describes the study protocol and its activities to date. Data collection was halted early because of COVID-19 restrictions on research activity, and data analysis is currently in progress. CONCLUSIONS: At the end of the project, we anticipate having an initial comparative evaluation of the SCREEN as a tool for early detection of MCI in primary care older adult patient populations. Resource constraints on this research study limit our ability to conduct a randomized controlled trial; however, the results will assist developers of the SCREEN in determining whether rigorous controlled testing is warranted. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25520.
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Contrave® is an adjunct pharmacotherapy for obesity that contains bupropion (BUP) and naltrexone (NTX). To further explore the psychopharmacology of this drug combination, male Sprague-Dawley rats were implanted with subcutaneous osmotic mini-pumps releasing: 40 mg/kg/day BUP, 4 mg/kg/day NTX, or 40 + 4 mg/kg/day BUP and NTX (BN). During 12 days of exposure, the animals were tested on operant intraoral self-administration (IOSA) of high fructose corn syrup (HFCS) on continuous (FR1) and progressive ratio (PR) schedules, on home cage drinking of HFCS, and on HFCS taste reactivity. Locomotion activity was also assessed. At the conclusion of the study, mRNA expression of genes involved in reward processing, appetite and mood were quantified. It was found that BN produced effects that could largely be ascribed to either BUP or NTX independently. More specifically, BN-induced reductions of HFCS IOSA on a FR1 schedule and home cage drinking, as well as alterations of MOR and POMC mRNA in the nucleus accumbens core and hypothalamus respectively, were attributable to NTX; while alterations of hippocampal BDNF mRNA was attributable to BUP. But, there was also some evidence of drug synergy: only BN caused persistent reductions of HFCS IOSA and drinking; BN produced the least gain of body weight; and only BN-treated rats displayed altered D2R mRNA in the caudate-putamen. Taken together, these observations support the use of BUP + NTX as a mean to alter consumption of sugars and reducing their impact on brain systems involved in reward, appetite and mood.
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Fármacos Antiobesidade/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Bupropiona/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Xarope de Milho Rico em Frutose , Naltrexona/farmacologia , Animais , Combinação de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Xarope de Milho Rico em Frutose/administração & dosagem , Masculino , Atividade Motora/efeitos dos fármacos , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Recompensa , AutoadministraçãoRESUMO
This study explored whether different ratios of fructose (F) and glucose (G) in sugar can engender significant differences in self-administration and associated neurobiological and physiological responses in male Sprague-Dawley rats. In Experiment 1, animals self-administered pellets containing 55% F + 45% G or 30% F + 70% G, and Fos immunoreactivity was assessed in hypothalamic regions regulating food intake and reward. In Experiment 2, rats self-administered solutions of 55% F + 42% G (high fructose corn syrup (HFCS)), 50% F + 50% G (sucrose) or saccharin, and mRNA of the dopamine 2 (D2R) and mu-opioid (MOR) receptor genes were assessed in striatal regions involved in addictive behaviors. Finally, in Experiment 3, rats self-administered HFCS and sucrose in their home cages, and hepatic fatty acids were quantified. It was found that higher fructose ratios engendered lower self-administration, lower Fos expression in the lateral hypothalamus/arcuate nucleus, reduced D2R and increased MOR mRNA in the dorsal striatum and nucleus accumbens core, respectively, as well as elevated omega-6 polyunsaturated fatty acids in the liver. These data indicate that a higher ratio of fructose may enhance the reinforcing effects of sugar and possibly lead to neurobiological and physiological alterations associated with addictive and metabolic disorders.
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Encéfalo/efeitos dos fármacos , Carboidratos da Dieta/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Frutose/farmacologia , Glucose/farmacologia , Animais , Comportamento Aditivo/etiologia , Carboidratos da Dieta/efeitos adversos , Sacarose Alimentar/farmacologia , Ácidos Graxos Ômega-6/metabolismo , Frutose/administração & dosagem , Glucose/administração & dosagem , Xarope de Milho Rico em Frutose/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Obesidade/etiologia , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Receptores Opioides mu/genética , Receptores Opioides mu/metabolismo , RecompensaRESUMO
This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e. 8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e. one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.
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Condicionamento Operante , Reforço Psicológico , Paladar , Animais , Comportamento Animal , Masculino , Ratos , Ratos Sprague-Dawley , AutoadministraçãoRESUMO
RATIONALE: There is evidence that pre-exposure to drugs of abuse can induce sensitization to several of their effects. OBJECTIVE: Four experiments were conducted to investigate the effect of heroin pre-exposure on modulation of memory consolidation as indexed by heroin's action on rate of learning. MATERIALS AND METHODS: Male Sprague-Dawley rats were tested on a social recognition learning task which assesses changes in investigation during repeated exposure to the same rat (habituation training: four sessions) and during exposure to a novel rat (dishabituation test). In the first experiment, rats received 0, 0.3, or 1 mg/kg heroin s.c. immediately following each training session, or 1 mg/kg heroin 2 h post-training. In experiments 2 and 3, rats received 1 mg/kg heroin post-training after a 7-day drug-free period from heroin pre-exposure achieved through conditioned place preference (1 mg/kg s.c., 1 injection/day x 4 days) or intravenous self-administration (0.05 mg/kg/infusion i.v., 3 h/day x 9 days) training. In experiment 4, rats received 0, 0.03, 0.3, or 3 mg/kg heroin post-training after a 7-day drug-free period from a regimen of heroin administration (i.e., 1 mg/kg heroin/day s.c. x 7 days) that induced locomotor sensitization. RESULTS: Post-training administration of heroin enhanced social recognition learning in a dose- and time-dependent manner. Importantly, no regimen of heroin pre-exposure significantly altered this effect of heroin. CONCLUSIONS: These results do not support the hypothesis that heroin pre-exposure leads to sensitization to its effect on memory consolidation of non-drug-related learning. However, this requires further testing using alternative heroin pre-exposure regimens, a wider range of post-training heroin doses, as well as other types of learning tasks.
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Heroína/farmacologia , Aprendizagem/efeitos dos fármacos , Entorpecentes/farmacologia , Reconhecimento Psicológico/efeitos dos fármacos , Comportamento Social , Animais , Aprendizagem por Associação/efeitos dos fármacos , Condicionamento Operante/efeitos dos fármacos , Relação Dose-Resposta a Droga , Habituação Psicofisiológica/efeitos dos fármacos , Dependência de Heroína/psicologia , Infusões Intravenosas , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , AutoadministraçãoRESUMO
To elucidate the effects of steady-state methadone exposure on responding to cocaine conditioned stimuli and on cocaine-induced alterations in central opioid, hypocretin/orexin, and D2 receptor systems, male Sprague-Dawley rats received intravenous infusions of 1 mg/kg/inf cocaine paired with an audiovisual stimulus over three days of conditioning. Then, mini pumps releasing vehicle or 30 mg/kg/day methadone were implanted (SC), and lever pressing for the stimulus was assessed in the absence of cocaine and after a cocaine prime (20 mg/kg, IP). It was found that rats treated with vehicle, but not methadone, responded for the cocaine conditioned stimulus and displayed elevated mu-opioid receptor mRNA expression in the nucleus accumbens core and basolateral amygdala, reduced hypocretin/orexin mRNA in the lateral hypothalamus, and reduced D2 receptor mRNA in the caudate-putamen. This is the first demonstration that steady-state methadone administered after cocaine exposure blocks cocaine-induced behavioral and neural adaptations.