165 research outputs found
cAMP Response Element-Binding Protein Deficiency Allows for Increased Neurogenesis and a Rapid Onset of Antidepressant Response
cAMP response element-binding protein (CREB) has been implicated in the molecular and cellular mechanisms of chronic antidepressant (AD) treatment, although its role in the behavioral response is unclear. CREB-deficient (CREBαΔ mutant) mice demonstrate an antidepressant phenotype in the tail suspension test (TST) and forced-swim test. Here, we show that, at baseline, CREBαΔ mutant mice exhibited increased hippocampal cell proliferation and neurogenesis compared with wild-type (WT) controls, effects similar to those observed in WT mice after chronic desipramine (DMI) administration. Neurogenesis was not further augmented by chronic DMI treatment in CREBαΔ mutant mice. Serotonin depletion decreased neurogenesis in CREBαΔ mutant mice toWTlevels, which correlated with a reversal of the antidepressant phenotype in the TST. This effect was specific for the reversal of the antidepressant phenotype in these mice, because serotonin depletion did not alter a baseline anxiety-like behavior in CREB mutant mice. The response to chronic AD treatment in the novelty-induced hypophagia (NIH) test may rely on neurogenesis. Therefore, we used this paradigm to evaluate chronic AD treatment in CREB mutant mice to determine whether the increased neurogenesis in these mice alters their response in the NIH paradigm. Whereas both WT and CREBαΔ mutant mice responded to chronic AD treatment in the NIH paradigm, only CREBαΔ mutant mice responded to acute AD treatment. However, in the elevated zero maze, DMI did not reverse anxiety behavior in mutant mice. Together, these data show that increased hippocampal neurogenesis allows for an antidepressant phenotype as well as a rapid onset of behavioral responses to AD treatment
Serotonin controlling feeding and satiety
Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and ‘true’ satiation and satiety. Currently, 5-HT1B, 5-HT2C and 5-HT6 receptors have been identified to mediate serotonergic satiety in different ways. The recently approved anti-obesity drug lorcaserin is a 5-HT2C receptor agonist. In brain, both hypothalamic (arcuate nucleus, paraventricular nucleus) and extrahypothalamic sites (parabrachial nucleus, nucleus of the solitary tract) have been identified to mediate the serotonergic control of satiety. Serotonin interacts within the hypothalamus with endogenous orexigenic (Neuropeptide Y/Agouti related protein) and anorectic (α-melanocyte stimulating hormone) peptides. In the nucleus of the solitary tract serotonin integrates peripheral satiety signals. Here, the 5-HT3, but possibly also the 5-HT2C receptor play a role. It has been found that 5-HT acts in concert with such peripheral signals as cholecystokinin and leptin. Despite the recent advances of our knowledge, many of the complex interactions between 5-HT and other satiety factors are not fully understood yet. Further progress in research will also advance the development of new serotonergic anti-obesity drugs
Relação entre o craving por tabaco e o craving por crack em pacientes internados para desintoxicação
Dinámica territorial de pueblos y localidades en Buenos Aires : Estudios de caso
Este trabajo es parte del Proyecto de investigación "Dinámica territorial en Buenos Aires. Cambios en el patrón de urbanización, usos del suelo e impactos socio-económicos y ambientales asociados". Se centra en algunas de las ciudades cabeceras de partidos con relación a ciertas localidades y pueblos que articulan social y territorialmente en el área de influencia de la Universidad Nacional de Luján, relacionado con la Región Metropolitana de Buenos Aires. El objetivo es analizar la dinámica territorial y ambiental de diversos espacios geográficos como consecuencia de los cambios en el patrón de urbanización, usos del suelo e impactos asociados. La metodología sigue las consideraciones de la Geografía crítica y de la Geografía de la percepción. Para ello, se requiere la articulación de múltiples variables teniendo en cuenta procesos y técnicas propias de la investigación social y ambiental, entre ellas: relevamiento bibliográfico, estadístico, jurídico y cartográfico. También búsqueda de información sobre los procesos históricos-geográficos y ambientales mediante diversas técnicas de obtención de datos primarios a través del trabajo de campo. En este sentido, se presentan los avances sobre transformaciones territoriales de algunas localidades de la provincia de Buenos Aires. Por un lado, los nuevos usos del suelo y las consecuencias espaciales y ambientales en las Villas de Portela y Santa Coloma en el Partido de Baradero y por otro lado, los efectos socio-territoriales de la construcción del tramo de la autopista Mercedes-Luján en barrios del Partido de Luján
Dinámica territorial de pueblos y localidades en Buenos Aires : Estudios de caso
Este trabajo es parte del Proyecto de investigación "Dinámica territorial en Buenos Aires. Cambios en el patrón de urbanización, usos del suelo e impactos socio-económicos y ambientales asociados". Se centra en algunas de las ciudades cabeceras de partidos con relación a ciertas localidades y pueblos que articulan social y territorialmente en el área de influencia de la Universidad Nacional de Luján, relacionado con la Región Metropolitana de Buenos Aires. El objetivo es analizar la dinámica territorial y ambiental de diversos espacios geográficos como consecuencia de los cambios en el patrón de urbanización, usos del suelo e impactos asociados. La metodología sigue las consideraciones de la Geografía crítica y de la Geografía de la percepción. Para ello, se requiere la articulación de múltiples variables teniendo en cuenta procesos y técnicas propias de la investigación social y ambiental, entre ellas: relevamiento bibliográfico, estadístico, jurídico y cartográfico. También búsqueda de información sobre los procesos históricos-geográficos y ambientales mediante diversas técnicas de obtención de datos primarios a través del trabajo de campo. En este sentido, se presentan los avances sobre transformaciones territoriales de algunas localidades de la provincia de Buenos Aires. Por un lado, los nuevos usos del suelo y las consecuencias espaciales y ambientales en las Villas de Portela y Santa Coloma en el Partido de Baradero y por otro lado, los efectos socio-territoriales de la construcción del tramo de la autopista Mercedes-Luján en barrios del Partido de Luján
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Kappa‐opioid receptors differentially regulate low and high levels of ethanol intake in female mice
Abstract Introduction: Studies in laboratory animals and humans indicate that endogenous opioids play an important role in regulating the rewarding value of various drugs, including ethanol (EtOH). Indeed, opioid antagonists are currently a front‐line treatment for alcoholism in humans. Although roles for mu‐ and delta‐opioid receptors have been characterized, the contribution of kappa‐opioid receptors (KORs) is less clear. There is evidence that changes in KOR system function can decrease or increase EtOH drinking, depending on test conditions. For example, female mice lacking preprodynorphin – the precursor to the endogenous KOR ligand dynorphin – have reduced EtOH intake. Considering that KORs can regulate dopamine (DA) transmission, we hypothesized that KORs expressed on DA neurons would play a prominent role in EtOH intake in females. Methods: We used a Cre/loxP recombination strategy to ablate KORs throughout the body or specifically on dopamine uptake transporter (DAT)‐expressing neurons to investigate the role of KORs on preference for and intake of EtOH (2‐bottle choice), the transition from moderate to excessive EtOH drinking (intermittent EtOH access), and binge EtOH drinking (drinking in the dark [DID]). Results: KOR deletion decreased preference for EtOH, although this effect was less pronounced when EtOH intake increased beyond relatively low levels. Discussion Our findings indicate that KOR activation increases EtOH drinking via effects mediated, at least in part, by KORs on DA neurons. While the mechanisms of this regulation remain unknown, previous work suggests that alterations in negative reinforcement processes or sensitivity to the sensory properties of EtOH can affect preference and intake
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