RESUMO
BACKGROUND: Inequity in health is a global concern. Even in Sweden there are considerable health gaps between different social groups, not least concerning life-style related conditions. Interventions drawing on Community-based participatory research (CBPR) have potential to build prerequisites for complex, supportive structures that constitute basis for implementation of sustainable health promoting programs. CBPR rests on principles of empowerment. The researchers are responsible for the scientific quality and that ethical standards are met. Health Equilibrium Initiative (HEI) aims at narrowing the health gap and promoting healthy weight in children; "healthy weight" including both anthropometric criteria and aspects having to do with self-esteem and self-efficacy. Evaluation objectives are to compare outcome between children in intervention and control areas, conduct health economic assessments (HEA) and evaluate the processes of the project. METHODS/DESIGN: HEI is a repeated cross-sectional and longitudinal study. The Program Logic Model is based on Social Cognitive Theory and Intervention Mapping. Primary contact groups are children in disadvantaged communities. Core efforts are to confirm and convey knowledge, elucidate and facilitate on-going health work and support implementation of continuous health work. Socioeconomic status is assessed on area level by the parameters yearly average income, degree of employment, tertiary education and percent of inhabitants born in countries where violent conflicts recently have taken place or were ongoing. Anthropometry, food patterns, physical activity and belief in ability to affect health; together with learning, memory and attention assessment will be assessed in 350 children (born 2006). Examinations will be repeated after two years, forming the basis of a health economic analysis. The process evaluation procedure will use document analysis (such as structured reports from meetings and dialogues, school/workplaces policies and curriculum, food service menus); key informant interviews and focus groups with parents, children and professionals. DISCUSSION: Inviting, awaiting and including local perspectives create mutual confidence and collaboration. Enhanced self-efficacy and access to relevant knowledge has potential to enable individuals and communities to choose alternatives that are relevant for their health and well-being in a long perspective. The economic of this study may contribute in decision- making processes regarding appropriate public health interventions.
Assuntos
Peso Corporal , Promoção da Saúde/métodos , Disparidades nos Níveis de Saúde , Avaliação de Programas e Projetos de Saúde/métodos , Saúde Pública/métodos , Criança , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , SuéciaRESUMO
Ecstasy, 3,4-methylenedioxymetamphetamine (MDMA), is a recreational drug used among adolescents, including young pregnant women. MDMA passes the placental barrier and may therefore influence fetal development. The aim was to investigate the direct effect of MDMA on cortical cells using dissociated CNS cortex of rat embryos, E17. The primary culture was exposed to a single dose of MDMA and collected 5 days later. MDMA caused a dramatic, dose-dependent (100 and 400 microM) decrease in nestin-positive stem cell density, as well as a significant reduction (400 microM) in NeuN-positive cells. By qPCR, MDMA (200 microM) caused a significant decrease in mRNA expression of the 5HT3 receptor, dopamine D(1) receptor, and glutamate transporter EAAT2-1, as well as an increase in mRNA levels of the NMDA NR1 receptor subunit and the 5HT(1A) receptor. In conclusion, MDMA caused a marked reduction in stem cells and neurons in embryonic cortical primary cell cultures, which was accompanied by changes in mRNA expression of specific receptors and transporters for glutamatergic and monoaminergic neurotransmitters.
Assuntos
Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Embrião de Mamíferos/citologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Neurônios/citologia , Células-Tronco/citologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Contagem de Células , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Células-Tronco/efeitos dos fármacos , Células-Tronco/enzimologiaRESUMO
BACKGROUND: GPR125 belongs to the family of Adhesion G protein-coupled receptors (GPCRs). A single copy of GPR125 was found in many vertebrate genomes. We also identified a Drosophila sequence, DmCG15744, which shares a common ancestor with the entire Group III of Adhesion GPCRs, and also contains Ig, LRR and HBD domains which were observed in mammalian GPR125. RESULTS: We found specific expression of GPR125 in cells of the choroid plexus using in situ hybridization and protein-specific antibodies and combined in situ/immunohistochemistry co-localization using cytokeratin, a marker specific for epithelial cells. Induction of inflammation by LPS did not change GPR125 expression. However, GPR125 expression was transiently increased (almost 2-fold) at 4 h after traumatic brain injury (TBI) followed by a decrease (approximately 4-fold) from 2 days onwards in the choroid plexus as well as increased expression (2-fold) in the hippocampus that was delayed until 1 day after injury. CONCLUSION: These findings suggest that GPR125 plays a functional role in choroidal and hippocampal response to injury.
Assuntos
Lesões Encefálicas/fisiopatologia , Plexo Corióideo/patologia , Proteínas de Membrana/genética , Receptores Acoplados a Proteínas G/genética , Animais , Sequência de Bases , Lesões Encefálicas/induzido quimicamente , Plexo Corióideo/metabolismo , Perfilação da Expressão Gênica , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Queratinas/genética , Queratinas/metabolismo , Lipopolissacarídeos , Masculino , Glicoproteínas de Membrana , Proteínas de Membrana/metabolismo , Camundongos , Complexo Glicoproteico GPIb-IX de Plaquetas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Receptores Acoplados a Proteínas G/metabolismo , Fatores de Tempo , Regulação para Cima/genéticaRESUMO
This study investigated GABA signaling following induction of behavioural sensitization to nicotine. Rats were repeatedly injected with saline, nicotine or hexamethonium for 18 days and gene expression was measured with qPCR. Nicotine upregulated GABAA alpha1 subunit expression in the nucleus accumbens (p<0.05) while no changes were observed for GABAA alpha3, alpha4 or alpha5. In the medial prefrontal cortex, no change in expression of the GABAA subunits was observed. We found that nicotine significantly decreased expression of the transporter GAT-1/SLC6A1 (p<0.05) in the medial prefrontal cortex while the expression of the GAT-3/SLC6A11 (p<0.05) transporter was increased in the nucleus accumbens. This provides the first evidence of neuroadaptive changes in the GABA system after nicotine sensitization and the first demonstration of an effect on GAT-1 or GAT-3 transporters in the addiction field. The GAT-1 findings also provide evidence for an alternative theory of why most schizophrenic individuals also use tobacco products.
Assuntos
Proteínas da Membrana Plasmática de Transporte de GABA/biossíntese , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Córtex Pré-Frontal/metabolismo , Animais , Primers do DNA , DNA Complementar/biossíntese , DNA Complementar/genética , Interpretação Estatística de Dados , Proteínas da Membrana Plasmática de Transporte de GABA/efeitos dos fármacos , Compostos de Hexametônio/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Neurotransmissores/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , RNA/biossíntese , RNA/genética , Ratos , Ratos Wistar , Receptores de GABA-A/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Self-administration of ethanol and food share many common features and Richter hypothesized that an increase in ethanol consumption would decrease feeding to balance the excess calories contained in the ethanol. Previously, we have shown that individual alcohol consumption correlates with neurotransmitter gene expression, especially in the prefrontal cortex. To test the hypothesis of Richter, we measured hypothalamic gene expression of receptors or neuropeptides of known relevance for the regulation of food intake using qPCR and correlated this to individual ethanol consumption in Wistar rats. For validation, gene expression was first correlated with body weight. We found a correlation of dynorphin, somatostatin, melanocortin-4 receptor and serotonin 5-HT(2C) with body weight and trends to correlation for CART, thus confirming the established role of the hypothalamus in the regulation of weight. For ethanol consumption, correlations were found for CRH receptors 1 and 2 and vasopressin while strong trends were observed for galanin receptor 1, orexin receptor 1, MCH and adrenoceptor alpha(1B). Therefore, alcohol consumption does seem to involve several hypothalamic systems which also mediate feeding responses and suggests that the hypothalamus, together with the prefrontal cortex, may determine the 'stopping point' of an individual.
Assuntos
Consumo de Bebidas Alcoólicas/genética , Hipotálamo/metabolismo , Neuropeptídeos/genética , Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/psicologia , Animais , Arginina Vasopressina/genética , Sequência de Bases , Peso Corporal/genética , Primers do DNA/genética , Ingestão de Alimentos/genética , Expressão Gênica , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/genética , AutoadministraçãoRESUMO
About half of the risk to develop alcoholism is related to genetic background and it is well known that alcohol consumption is highly individualized. In this study, we investigated how individual alcohol consumption behaviour in Wistar rats correlated with mRNA expression of 20 genes in the prefrontal cortex, hippocampus and amygdala. We found that the long-term alcohol consumption of an individual could be estimated by the mean of its consumption on Day 2 and 3. This short exposure minimized changes in gene expression induced by alcohol itself. We found a positive correlation in the prefrontal cortex of GABA(A) alpha5 (r=0.96), GABA(B1) (r=0.96), AMPA GluR1 (r=0.93), 5-HT(3A) (r=0.93) and the alpha adrenoceptors (alpha(1A)r=1.00, alpha(1B)r=0.93, alpha(2A)r=0.93) with consumption. In the hippocampus, we found negative correlations with the NMDA NR2A subunit (r=-0.86), the alpha(1A) adrenoceptor (r=-0.89) and the glucocorticoid receptor (r=-0.86). Finally, in the amygdala there was a negative correlation to NMDA NR2A (r= -0.79) and a positive correlation with serotonin 5-HT(2C) (r=0.79). In conclusion, we have used qPCR to identify specific genes in the brain that correlated to alcohol self-administration of an individual animal. This study suggests that alcohol consumption in the early stages of acquisition depends on the genetic background of the individual and that the prefrontal cortex is particularly important in this behaviour.
Assuntos
Consumo de Bebidas Alcoólicas/genética , Tonsila do Cerebelo/metabolismo , Hipocampo/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de Neurotransmissores/genética , Animais , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Primers do DNA , DNA Complementar/biossíntese , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Expressão Gênica/fisiologia , Masculino , RNA/biossíntese , RNA/isolamento & purificação , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sacarina/farmacologiaRESUMO
In a previous report, we found that a 5-min. delay in alcohol access increases ethanol intake in rats trained to self-administer 5% ethanol. To assess the effects of this delay on the motivation to self-administer ethanol, Wistar rats were trained on a progressive ratio schedule of reinforcement and presented with the 5-min. delay. There was no change in break point (6 presses/delivery), active (125 presses/30 min.) or inactive (10 presses/30 min.) lever presses after the 5-min. delay compared to baseline. However, response cessation occurred 10 min. earlier in this delay session compared to baseline indicating that consumption was accelerated by delayed access to alcohol.
Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Depressores do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Tempo de Reação , Esquema de Reforço , Animais , Masculino , Motivação , Ratos , Ratos Wistar , Autoadministração/psicologiaRESUMO
Stress early in life puts the individual at a greater risk for developing mental disorders in adulthood. The animal model of maternal separation involves daily removal of pups from their mother over the early postnatal period and leads to several behavioral deficits in adults. Since this period corresponds to a time of extensive developmental changes in the glutamatergic system, glutamate receptor mRNA expression was studied in the hippocampus and prefrontal cortex. Male Wistar rats were either separated from their mother for 15 min (MS15 or 'handling') or 360 min (MS360) once a day from pnd 1-21 and glutamate receptor expression levels were measured at 25 weeks of age using real-time RT-PCR analysis. A third group of animal facility reared (AFR) rats was included as a control for the handling group. In the hippocampus, mRNA expression of NMDA NR2B and AMPA GluR1 and GluR2 receptors was significantly lower in MS360 rats relative to MS15. In addition, expression of the glutamate transporter GLAST was increased in MS360 relative to MS15. No differences were observed for AFR rats relative to MS15, which indicates that the hippocampal effects were not a result of handling or maternal care. For the prefrontal cortex, no difference in mRNA expression was observed for NMDA NR2A and NR2B or AMPA GluR1 and GluR2. These findings suggest that prolonged maternal separation produces neuroadaptive changes in the hippocampus that may, at least partially, account for the behavioral deficits previously observed in this animal model.
Assuntos
Regulação da Expressão Gênica/fisiologia , Hipocampo/metabolismo , Privação Materna , Córtex Pré-Frontal/metabolismo , Receptores de Glutamato/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Feminino , Hipocampo/crescimento & desenvolvimento , Masculino , Córtex Pré-Frontal/crescimento & desenvolvimento , Gravidez , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Glutamato/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
Cognitive impairments are observable in over half of cases with alcoholism, deficits in spatial working memory being particularly common. Previously we observed that rats make more alternation errors in a Y-maze test of spontaneous alternation behaviour/spatial working memory after 5-day intermittent ethanol. Here we used qPCR to quantify changes in gene expression accompanying this behavioural impairment. Male Wistar rats were treated with either saline or ethanol (1 or 2.5g/kg) for 5days followed by 2 drug-free days. Brains were dissected after Y-maze analysis and RNA was extracted from the medial prefrontal cortex, hippocampus and nucleus accumbens. Using the Qiagen GABA & Glutamate PCR array we measured changes in these two neurotransmitter systems. A dose of 1g/kg ethanol did not affect spontaneous alternation behaviour or any other behavioural variable. 2.5g/kg significantly decreased % correct alternations (p=0.028) without affecting total distance (p=0.54) and increased time in the choice area (p=0.023) at the Y-maze centre, indicating a possible impairment in decision-making. In the medial prefrontal cortex, 2.5g/kg ethanol decreased mRNA expression of brain-derived neurotrophic factor, NMDA NR2A subunit, mGluR8 receptor, Homer1, the glutamate transporters SLC1a1 and SLC1a6 and Srr. In the nucleus accumbens this dose did not affect mRNA expression of the dopamine D1 or D2 receptors but did upregulate the GABA transporter GAT-3. Even if only correlational, these data suggest that gene expression changes in the medial prefrontal cortex and associated cognitive impairment occur before adaptation of the dopaminergic system and, presumably, drug dependence.
RESUMO
RATIONALE: Alcohol-associated cues elicit craving in human addicts but little is known about craving mechanisms. Current animal models focus on relapse and this may confound the effect of environmental cues. OBJECTIVES. To develop a model to study the effects of environmental cues on alcohol consumption in animals not experiencing withdrawal or relapse. METHODS: Rats were trained to orally self-administer an alcohol (5% w/v)/saccharin (0.2%) solution 30 min a day for 20 days. After stable responding on a free choice between alcohol/saccharin and water, rats were exposed to 5, 10 or 15 min of alcohol-associated cues or 5 min of non-alcohol associated cues. The effect of a 5-min cue was measured after a 10-day break from training or pre-treatment with 0.03, 0.1 or 1 mg/kg naltrexone. RESULTS: Rats given 5 min of alcohol-associated cues responded significantly more on the active lever (26% increase) and consumed more alcohol as verified by increased blood alcohol levels (8.9 mM versus control 7.5 mM). Ten or 15 min of cues did not change alcohol consumption and 5 min in a novel environment decreased response by 66%. After a 10-day break in training, 5 min of alcohol-associated cues still increased alcohol consumption (29% increase) and the cue effect could be dose-dependently blocked by naltrexone (143% decrease at 0.03 mg/kg). CONCLUSIONS: Cue-induced behavioural activation was specific to alcohol cues, reproducible, persistent and could be blocked by naltrexone, and its correlation with human self-report of craving makes it a potentially useful model for studying alcohol craving.
Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Comportamento Aditivo/psicologia , Sinais (Psicologia) , Modelos Psicológicos , Animais , Aprendizagem por Discriminação , Meio Ambiente , Etanol/sangue , Masculino , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Ratos , Ratos Wistar , Reforço Psicológico , Autoadministração , Fatores de TempoRESUMO
BACKGROUND: "Clubs against drugs" (CAD) is a comprehensive program with a systems approach to prevention with the intention of preventing drug use in nightclub environment. In 2001 CAD was developed and implemented in Stockholm and was disseminated to 20 other municipalities in Sweden up until 2010. This study investigates the factors related to the implementation and compares Stockholm to the rest of the municipalities. METHODS: A sequential exploratory method was used which consisted of three steps including a questionnaire and two rounds of interviews. Questionnaires included all communities and the interviews included twelve respondents from three example municipalities in the first phase and four respondents from Stockholm in the second phase. The interviews were analyzed using content analysis. RESULTS: In Stockholm the program was described as having been implemented and sustained over time. The implementation in the example municipalities was perceived as difficult with many obstacles and achieving sustainability was also described as difficult. Two of three municipalities were not active at the time of this study, illustrating that the program only lasted a few years. Factors identified as being related to implementation outcomes were need assessments, participation, support, collaboration and local enthusiasts. CONCLUSIONS: The capacity to implement and sustain CAD differed substantially between Stockholm and the other municipalities. If the prerequisites and capacity are not sufficient the implementation is not likely to be successful, even when the activities are promoted on a national level like CAD. The needs of the interventions and the capacity to implement the program should be examined before adopting the program. This was not done, probably because the drive to spread the activity was not sufficiently questioned.
Assuntos
Meio Ambiente , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Cidades , Humanos , Avaliação das Necessidades , SuéciaRESUMO
Phencyclidine (PCP) mimics many aspects of schizophrenia, yet the underlying mechanism of neurochemical adaptation for PCP is unknown. We therefore used proteomics to study changes in the medial prefrontal cortex in animals with PCP-induced behavioural deficits. Male Wistar rats were injected with saline or 5 mg/kg phencyclidine for 5 days followed by two days of washout. Spontaneous alternation behaviour was tested in a Y-maze and then proteins were extracted from the medial prefrontal cortex. 2D-DIGE analysis followed by spot picking and protein identification with mass spectrometry then provided a list of differentially expressed proteins. Treatment with 5 mg/kg phencyclidine decreased the percentage of correct alternations in the Y-maze compared to saline-treated controls. Proteomics analysis of the medial prefrontal cortex found upregulation of 6 proteins (synapsin-1, Dpysl3, Aco2, Fscn1, Tuba1c, and Mapk1) and downregulation of 11 (Bin1, Dpysl2, Sugt1, ApoE, Psme1, ERp29, Pgam1, Uchl1, Ndufv2, Pcmt1, and Vdac1). A trend to upregulation was observed for Gnb4 and Capza2, while downregulation trends were noted for alpha-enolase and Fh. Many of the hits in this study concur with recent postmortem data from schizophrenic patients and this further validates the use of phencyclidine in preclinical translational research.
RESUMO
Prolonged consumption of ethanol produces prefrontal cortex (PFC) dysfunction in patients, and this has been demonstrated using structural, physiological and psychological measurements. We therefore wanted to develop an animal model of PFC dysfunction to study whether this state changes sensitivity for ethanol or other behavioural/motivational measures. Adolescent Wistar rats were first screened in the novel object recognition task to establish a pre-treatment baseline measure of locomotor activity, anxiety-like behaviour and PFC function. Animals were divided into four treatment groups [saline, 5 mg/kg phencyclidine (PCP), 2.5g/kg ethanol, ethanol + PCP] and injected i.p. for 5 days followed by a 2-day washout. On the 8th day, animals were allowed to explore a Y-maze for 10 min. and spontaneous alternations were recorded using the ANY-maze tracking system. PCP, a classic drug used to induce PFC dysfunction in animals, did not significantly reduce the % correct alternations relative to the 70% level achieved by the saline group. Ethanol and the combination of Ethanol + PCP, however, significantly reduced alternations to approximately 30%. The combined dose was not additive in terms of Y-maze impairment, and these animals had less total distance travelled and greater time immobile relative to the other groups. We therefore concluded that injection of 2.5 g/kg ethanol for 5 days in Wistar rats produces a more substantial, consistent and valid PFC dysfunction than 5 mg/kg PCP.
Assuntos
Comportamento Animal/efeitos dos fármacos , Etanol/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Fenciclidina/toxicidade , Animais , Modelos Animais de Doenças , Esquema de Medicação , Etanol/administração & dosagem , Alucinógenos/administração & dosagem , Alucinógenos/toxicidade , Masculino , Atividade Motora/efeitos dos fármacos , Fenciclidina/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/patologia , Ratos , Ratos WistarRESUMO
Glycine receptors (GlyRs) are pentameric membrane proteins in the form of either α-homomers or α-ß heteromers. Four out of five subunits; α1-3 and ß, have been found in the mammalian brain. Early studies investigating subunit composition and expression patterns of this receptor have proposed a developmental switch from α2 homomers to α1ß heteromers as the CNS matures, a conclusion primarily based on results from the spinal cord. However, our previous results indicate that this might not apply to e.g. the forebrain regions. Here we examined alterations in GlyR expression caused by developmental changes in selected brain areas, focusing on reward-related regions. Animals of several ages (P2, P21 and P60) were included to examine potential changes over time. In accordance with previous reports, a switch in expression was observed in the spinal cord. However, the present results indicate that a decrease in α2 subunit expression is not replaced by α1 subunit expression since the generally low levels, and modest increases, of α1 could hardly replace the reduction in α2-mRNA. Instead mRNA measurements indicate that α2 continues to be the dominating α-subunit also in adult animals, usually in combination with high and stable levels of ß-subunit expression. This indicates that alterations in GlyR subunit expression are not simply a maturation effect common for the entire CNS, but rather a unique pattern of transition depending on the region at hand.
Assuntos
Envelhecimento , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Prosencéfalo/crescimento & desenvolvimento , Prosencéfalo/metabolismo , Subunidades Proteicas/metabolismo , Receptores de Glicina/metabolismo , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Feminino , Masculino , Subunidades Proteicas/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Glicina/genéticaRESUMO
Maternal separation (MS) early in life affects many aspects of development and we have previously observed significant decreases in NMDA and AMPA receptor and elevated glutamate transporter expression in the hippocampus of MS360 animals relative to MS15. We hypothesized that this disruption of the glutamatergic system in adult animals was a sign of a reduction in hippocampal neuronal number in 3-week-old animals. Male Wistar rat pups were separated litter-wise for 15 min (MS15) or 360 min (MS360) from postnatal day 1 to 21. Conventional laboratory reared animals were also included. At postnatal day 22, brains were dissected and sliced on a cryostat. Immunohistochemistry labeled neurons (NeuN) and astrocytes (GFAP) and the number of neurons was quantified using the disector method and Cavalieri principle for stereology for the CA1, CA2, CA3 and dentate gyrus regions of the hippocampus. The volume of 4 regions did not differ across the 3 experimental groups. Numerical density of neurons, however, was significantly different in CA3 (one-way ANOVA; p=0.044) and the dentate gyrus (one-way ANOVA; p<0.0001) with post hoc differences MS360 vs. MS15. Finally, the total number of neurons was calculated and MS360 animals had significantly fewer neurons than MS15 animals in the dentate gyrus. Therefore, the maternal separation procedure affected development of the hippocampus directly at 3 weeks of age. The differences observed consequently place young MS360 animals in a vulnerable state for challenges later in life.
Assuntos
Ansiedade de Separação/patologia , Giro Denteado/patologia , Mães , Neurônios/patologia , Animais , Contagem de Células , Masculino , Ratos , Ratos WistarRESUMO
Executive dysfunction is a common symptom among alcohol-dependent individuals. Phencyclidine (PCP) injection induces dysfunction in the prefrontal cortex of animals but little is known about how PCP affects the response to ethanol. Using the in vivo microdialysis technique in male Wistar rats, we investigated how systemic injection of 5 mg/kg PCP would affect the dopamine release induced by local infusion of 300 mM ethanol into the nucleus accumbens. PCP given 60 min before ethanol entirely blocked ethanol-induced dopamine release. However, when ethanol was administered 60 min before PCP, both drugs induced dopamine release and PCP's effect was potentiated by ethanol (180% increase vs 150%). To test the role of prefrontal cortex dysfunction in ethanol reinforcement, animals were pretreated for 5 days with 2.58 mg/kg PCP according to previously used 'PFC hypofunction protocols'. This, however, did not change the relative response to PCP or ethanol compared to saline-treated controls. qPCR illustrated that this low PCP dose did not significantly change expression of glucose transporters Glut1 (SLC2A1) or Glut3 (SLC2A3), monocarboxylate transporter MCT2 (SLC16A7), glutamate transporters GLT-1 (SLC1A2) or GLAST (SLC1A3), the immediate early gene Arc (Arg3.1) or GABAergic neuron markers GAT-1 (SLC6A1) and parvalbumin. Therefore, we concluded that PCP at a dose of 2.58 mg/kg for 5 days did not induce hypofunction in Wistar rats. However, PCP and ethanol do have overlapping mechanisms of action and these drugs differentially affect mesolimbic dopaminergic transmission depending on the order of administration.
RESUMO
The beneficial effect of the '1-drink-a-day' lifestyle is suggested by studies of cardiovascular health, and this recommendation is increasingly followed in many countries. The main objective of this study was to determine whether this pattern of ethanol use would be detrimental to a pregnant woman. We exposed a primary culture of rat cerebellum from embryonic day 17 (corresponding to second trimester in humans) to ethanol at a concentration of 17.6 mM which is roughly equivalent to one glass of wine. Acutely, there was no change in cell viability after 5 or 8 days of exposure relative to control. By 11 days, a reduction in the number of viable cells was observed without an accompanying change in caspase-3 activity (marker of apoptotic cell death), suggesting changes in cell proliferation. As the proportion of nestin-positive cells was higher in the ethanol-treated cultures after 5 days, we hypothesized that an increase in differentiation to neurons would compensate for the ongoing neuronal death. However, there were limits to this compensatory ability as the relative proportion of nestin-positive cells was decreased after 11 days. To further illustrate the negative long-term effects of this ethanol dose, cultures were exposed for 30 days. After this period, virtually no neurons or myelinating oligodendrocytes were present in the ethanol-treated cultures. In conclusion, chronic exposure to ethanol, even at small doses, dramatically and persistently affects normal development.
Assuntos
Cerebelo/efeitos dos fármacos , Etanol/toxicidade , Neurônios/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cerebelo/citologia , Cerebelo/embriologia , Etanol/administração & dosagem , Feminino , Humanos , Proteínas de Filamentos Intermediários/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Nestina , Neurônios/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
INTRODUCTION: Vulnerability for weight gain is an individual trait. Obese people undertake dieting, but permanent weight loss is difficult to attain due to repeated phases of relapse to excess consumption. MATERIALS AND METHODS: In this study, male Wistar rats were trained to operantly self-administer pellets followed by free-choice access in the homecage to high-fat high-sugar (HFHS) diet consisting of 30% sucrose, lard, standard rodent chow and water. Animals were divided into obesity-prone (OP) and obesity-resistant (OR) groups based on relative weight gain compared to normally fed controls despite equal consumption of HFHS. RESULTS AND DISCUSSION: After 4 weeks of HFHS access, OP and OR animals did not differ in motivation for food pellets in terms of progressive ratio break point, lever pressing or response rate. However, upon discontinuation of the HFHS diet, differences between the OP and OR groups were noted. OP animals increased their motivation (i.e. craving) during the second withdrawal week and reduced time spent in the centre of an open field (increased anxiety) compared to the OR animals. Both OP and OR animals consumed less of the standard rodent chow during the first week of withdrawal when compared to normally fed controls. But, while the OR animals quickly returned to control levels of food consumption, OP animals continued to consume less standard rodent chow. CONCLUSION: The results show for the first time that withdrawal from free-choice HFHS induces craving that is specific to the OP animals and suggests that OP individuals may have withdrawal symptoms that are similar to those induced by addictive drugs.
Assuntos
Carboidratos/farmacologia , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Ingestão de Energia/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Obesidade/psicologia , Animais , Condicionamento Operante/efeitos dos fármacos , Interpretação Estatística de Dados , Dieta , Ingestão de Alimentos/efeitos dos fármacos , Masculino , Motivação , Ratos , Ratos Wistar , Esquema de Reforço , Recompensa , Aumento de Peso/efeitos dos fármacosRESUMO
Early environment is a known determinant for individual differences in vulnerability for adult psychopathology, e.g., ethanol addiction. One underlying mechanism could be dysfunction in serotonergic neurotransmission. This study focused on the methodological considerations regarding an animal model for studying effects of early environment, maternal separation (MS), using two different paradigms. Age- and sex-specific effects on brain stem 5-hydroxytryptamine (5-HT) transporter and receptors were examined. Male and female rat pups were assigned to either litter-wise MS for 15 or 360 min (MS15l or MS360l) or individual MS for 15 or 360 min (MS15i or MS360i) daily during postnatal days 1-21. Normal animal facility reared rats were used as controls. Analyses were performed in young and adult rats. As compared to the other males, MS15l males had lower 5-HT(1A) and 5-HT(2C) receptor mRNA expression at both ages, lower 5-HT(2A) receptor mRNA when young and lower 5-HTT mRNA expression when adult. In contrast, adult MS15l females had higher 5-HT(2C) receptor mRNA expression than other female rats. The strong impact of MS15l on 5-HT-related genes was either transient or persistent depending on sex and fewer effects on gene expression were observed in females than in males. This study shows the importance of tactile contact for the consequences of short but not prolonged MS, as evidenced by major differences between MS15l and MS15i. The results suggest that MS15i is less suitable than MS15l to simulate a protective environment in studies of, for instance, ethanol addiction processes.
Assuntos
Envelhecimento/metabolismo , Encéfalo/metabolismo , Privação Materna , Receptores de Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Caracteres Sexuais , Animais , Ciclo Estral/metabolismo , Feminino , Masculino , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Receptor 5-HT2C de Serotonina/metabolismo , Receptores 5-HT3 de Serotonina/metabolismo , Isolamento Social , Fatores de TempoRESUMO
Anxiety has been implicated in obesity and in the overconsumption of highly palatable foods such as those high in fat, sugar, or both. Also, the novelty-seeking trait has been associated with failure in weight-loss programs. The aim of this study was to investigate the associations of experimental anxiety and the self-administration of sucrose and high fat pellets in non-food deprived rats across different operant schedules. Male Wistar rats were subjected to the elevated plus-maze test (EPM) of anxiety-like behavior. The rats were tested for fixed ratio 5 (FR5) and progressive ratio (PR) operant responding for 50% sucrose, 95% sucrose, and high-fat pellets. PR active lever press response for 95% sucrose, but not the other pellet types, was correlated to % time spent on open arms (P=0.019) in the EPM. On the FR5 schedule, activity (closed arm entries) was correlated to the self-administration of 50% sucrose (P=0.027) and high-fat (P=0.002). This indicates an association of novelty-induced activity and self-administration of palatable food in sated rats, as well as a specific association of PR lever press response for 95% sucrose and low anxiety-like behavior. It has been argued that such active lever press response on PR may be interpreted as craving for the reinforcer; thus, our findings indicate an inverse relationship of experimental anxiety and craving for sucrose. This connection may have implications for human situations, since anxiety and novelty-seeking have been associated with obesity and failure in weight-loss programs.