Animal models of alcohol and drug dependence

Drug addiction has serious health and social consequences. In the last 50 years, a wide range of techniques have been developed to model specific aspects of drug-taking behaviors and have greatly contributed to the understanding of the neurobiological basis of drug abuse and addiction. In the last two decades, new models have been proposed in an attempt to capture the more genuine aspects of addiction-like behaviors in laboratory animals. The goal of the present review is to provide an overview of the preclinical procedures used to study drug abuse and dependence and describe recent progress that has been made in studying more specific aspects of addictive behavior in animals.Universidade Estadual Paulista School of Pharmaceutical SciencesUniversidade Estadual Paulista School of Pharmaceutical Science

Possible adverse drug events leading to hospital admission in a Brazilian teaching hospital

OBJECTIVES: Drug safety problems can lead to hospital admission. In Brazil, the prevalence of hospitalization due to adverse drug events is unknown. This study aims to estimate the prevalence of hospitalization due to adverse drug events and to identify the drugs, the adverse drug events, and the risk factors associated with hospital admissions. METHOD: A cross-sectional study was performed in the internal medicine ward of a teaching hospital in São Paulo State, Brazil, from August to December 2008. All patients aged ≥18 years with a length of stay ≥24 hours were interviewed about the drugs used prior to hospital admission and their symptoms/complaints/causes of hospitalization. RESULTS: In total, 248 patients were considered eligible. The prevalence of hospitalization due to potential adverse drug events in the ward was 46.4%. Overprescribed drugs and those indicated for prophylactic treatments were frequently associated with possible adverse drug events. Frequently reported symptoms were breathlessness (15.2%), fatigue (12.3%), and chest pain (9.0%). Polypharmacy was a risk factor for the occurrence of possible adverse drug events. CONCLUSION: Possible adverse drug events led to hospitalization in a high-complexity hospital, mainly in polymedicated patients. The clinical outcomes of adverse drug events are nonspecific, which delays treatment, hinders causality analysis, and contributes to the underreporting of cases

Influência do fumo na atividade da amilase salivar e na curva glicêmica Influence of smoking on salivary amylase activity and glycemic curve

OBJETIVO: Determinar a atividade da amilase salivar e a relação com a glicemia, antes e após a ingestão de carboidratos em fumantes e não fumantes, uma vez que in vitro a exposição da saliva à fumaça do cigarro induz à redução da atividade da amilase salivar e poderia influenciar na absorção dos carboidratos da dieta. MÉTODOS: Foram avaliados voluntários fumantes (n=10) e não fumantes (n=10). Realizou-se coletas da saliva antes e após o fumo e determinou-se a glicemia antes e após a ingestão de 72g de carboidratos. Para glicemia usaram-se tempos de 0, 15, 30, 60, 120 minutos. A determinação da atividade da amilase salivar foi realizada por meio de kits comerciais. A glicemia foi determinada utilizando o aparelho Glicomiter (Accu-Chek-Roche). As análises estatísticas foram realizadas no software Sigmastat, utilizou-se o método Teste t pareado (p<0,05). RESULTADOS: O aumento da glicemia aos 15, 30, 60 e 90 minutos foi de 3,9; 11,9; 34,8 e 22,7% para os não fumantes e 4,9; 6,5; 13,8 e 9,7% para os fumantes, respectivamente. No pico máximo de absorção tem-se uma glicemia de 21,0 % maior nos pacientes não fumantes. A atividade da amilase salivar antes e após alimentação apresentou-se 75,0% menor nos indivíduos fumantes. CONCLUSÃO: Estes resultados sugerem que o fumo inibe a amilase e influencia na diminuição da digestão/absorção de carboidratos, consequentemente na concentração de glicose sanguínea, reduzindo assim o aporte energético ingerido.<br>OBJECTIVE: The objective of this study was to determine salivary amylase activity and its relationship with glycemia before and after smokers and nonsmokers ingested carbohydrates. Since cigarette smoke reduces salivary amylase activity in vitro, it may affect dietary carbohydrate absorption. METHODS: Twenty volunteers participated in this study, 10 smokers and 10 nonsmokers. Samples of saliva were collected before and after the smokers had a cigarette and glycemia was determined before and after the ingestion of 72g of carbohydrates. Glycemia was measured 0, 15, 30, 60 and 120 minutes after carbohydrate intake. Salivary amylase activity was determined by commercial kits. Glycemia was determined by a glucometer (Accu-Chek-Roche). The paired t-test was used for the statistical analyses, done by the software Sigmastat, with p<0.05. RESULTS: Glycemia 15, 30, 60 and 90 minutes after carbohydrate intake rose 3.9%, 11.9%, 34.8% and 22.7% in nonsmokers and 4.9%, 6.5%, 13.8% and 9.7% in smokers, respectively. The peak glucose absorption in nonsmokers was 21.0% greater than in smokers. Salivary amylase activity before and after eating was 75.0% smaller in smokers. CONCLUSION: These results suggest that smoking inhibits amylase and has a negative impact on the digestion/absorption of carbohydrates, consequently in blood glucose levels, thereby reducing the amount of energy absorbed

Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice

Adverse early-life conditions induce persistent disturbances that give rise to negative emotional states. Therefore, early life stress confers increased vulnerability to substance use disorders, mainly during adolescence as the brain is still developing. In this study, we investigated the consequences of maternal separation, a model of maternal neglect, on the psychotropic effects of cocaine and the neuroplasticity of the dopaminergic system. Our results show that mice exposed to maternal separation displayed attenuated behavioural sensitization, while no changes were found in the rewarding effects of cocaine in the conditioned place preference paradigm and in the reinforcing effects of cocaine in the self-administration paradigm. The evaluation of neuroplasticity in the striatal dopaminergic pathways revealed that mice exposed to maternal separation exhibited decreased protein expression levels of D2 receptors and increased levels of the transcriptional factor Nurr1. Furthermore, animals exposed to maternal separation and treated with cocaine exhibited increased DA turnover and protein expression levels of DAT and D2R, while decreased Nurr1 and Pitx3 protein expression levels were observed when compared with saline-treated mice. Taken together, our data demonstrate that maternal separation caused an impairment of cocaine-induced behavioural sensitization possibly due to a dysfunction of the dopaminergic system, a dysfunction that has been proposed as a factor of vulnerability for developing substance use disorders.This study was supported by UE MedBioinformatics project (Grant Agreement Number: 634143), MINECO (SAF2013-41761-R-FEDER and SAF2013-49076-P-FEDER), Spanish Ministry of Health (Retic-ISCIII-RD/12/0028/0024-FEDER and RETICS-ISCIII-RD 12/0028/003-FEDER and Plan Nacional sobre Drogas 2014/020), Generalitat de Catalunya (2014SGR34) and Fundación Séneca (15405/PI/10), Región de Murcia. IG-R was funded by FPI fellowship BES-2011-046655 associated to SAF2010-15793