Involvement of dopamine receptors in diethylpropion-induced conditioning place preference

Diethylpropion (DEP) is an amphetamine-like agent used as an anorectic drug. Abuse of DEP has been reported and some restrictions of its use have been recently imposed. The conditioning place preference (CPP) paradigm was used to evaluate the reinforcing properties of DEP in adult male Wistar rats. After initial preferences were determined, animals weighing 250-300 g (N = 7 per group) were conditioned with DEP (10, 15 or 20 mg/kg). Only the dose of 15 mg/kg produced a significant place preference (358 ± 39 vs 565 ± 48 s). Pretreatment with the D1 antagonist SCH 23390 (0.05 mg/kg, sc) 10 min before DEP (15 mg/kg, ip) blocked DEP-induced CPP (418 ± 37 vs 389 ± 31 s) while haloperidol (0.5 mg/kg, ip), a D2 antagonist, 15 min before DEP was ineffective in modifying place conditioning produced by DEP (385 ± 36 vs 536 ± 41 s). These results suggest that dopamine D1 receptors mediate the reinforcing effect of DE

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