Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin.

Despite the apparent abundance of ligand-gated transient receptor potential vanilloid type 1 (TRPV1) and possible cross talk between the endocannabinoid and endovanilloid systems in the central nervous system (CNS), it is unclear what role TRPV1 receptor activation in CNS plays in neurobehavioral development. We previously reported that capsaicin or WIN55212-2 induces risk aversion in the plus-maze test, which was dependent on the gender and mouse strain used. In this study, pregnant BALBc mice were administered capsaicin (1.0 or 4.0 mg/kg, i.p.) during the second week of gestation. Developmental effects of prenatal exposure to capsaicin were assessed in neonates, and behavioral effects were assessed in adult offspring. Gender- and dose-specific variations in ultrasonic vocalizations, weight gain, righting reflex, and general activity of the pups were observed. Prenatal exposure to capsaicin altered plus-maze performance, especially with further exogenous capsaicin challenge. Furthermore, dose- and gender-specific effects were evident in the conditioned place preference/aversion paradigm following conditioning with capsaicin in adult animals. The capsaicin-induced aversion in the plus-maze test was enhanced by WIN55212-2 and blocked by pretreatment with vanilloid antagonist capsazepine or the CB1 receptor antagonist rimonabant, demonstrating an interaction between the endocannabinoid and endovanilloid systems in CNS. Taken together, the interaction between the endocannabinoid and endovanilloid signaling systems can be exploited for therapeutic applications in health and disease.

Functional expression of brain neuronal CB2 cannabinoid receptors are involved in the effects of drugs of abuse and in depression.

Major depression and addiction are mental health problems associated with stressful events in life with high relapse and recurrence even after treatment. Many laboratories were not able to detect the presence of CB2 cannabinoid receptors (CB2-Rs) in healthy brains, but CB2-R expression has been demonstrated in rat microglial cells and other brain-associated cells during inflammation. Thus, neuronal expression of CB2-Rs has been ambiguous and controversial, and its role in depression and substance abuse is unknown. In this study we tested the hypothesis that genetic variants of the CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances, including opiates, cocaine, and ethanol, in rodents. Here we demonstrate that a high incidence of Q63R but not H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated after exposure to stressors and administration of abused drugs. Mice that developed an alcohol preference had reduced CB2 gene expression, and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 antisense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. Using electron microscopy we report the subcellular localization of CB2-Rs that are mainly on postsynaptic elements in rodent brain. Our data demonstrate the functional expression of CB2-Rs in the brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuroimmunocannabinoid activity.

Calidad de la imagen radiográfica abdominal en píelo grafía intravenosa / Quality of the image abdominal radiográfica in tweets him intravenous graph

La pielografía intravenosa es considerada como una pieza importante en el abordaje de la patología del tracto urinario. Su precisión diagnóstica depende en parte, de la calidad de la imagen radiográfica, motivo por el cual ésta debe evaluarse con el fin de favorecer un diagnóstico seguro y confiable, con valores de dosis de radiación razonables para el paciente.Con tal propósito se realizó un estudio descriptivo, retrospectivo, transversal en el Departamento de Radiología del Hospital Dr. Roberto Calderón G., sobre el cumplimiento de los criterios de calidad de la imagen radiográfica del abdomen para pielografía intravenosa, llevado a cabo durante l período de Julio a Diciembre del año 2007. Se tomó una muestra de 65 estudios que cumplieron los criterios de inclusión, realizando lectura de las radiografías con un índice muy bueno de confiabilidadintraobservador de 0.85, e interobservador de 0.82.Se encontró que los criterios de posicionamiento y los referidos a la información diagnóstica de las proyecciones de abdomen cumplen con los requisitos básicos de calidad de imagen para su interpretación dentro de parámetros aceptables, permiten la identificación de detalles necesarios que posibiliten una adecuada interpretación de las patologías presentes. Sin embargo, la radiación recibida porel paciente posiblemente sea mayor a los parámetros de referencia. Laaceptabilidad de nuestros estudios está dentro de límites adecuados...

Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.

BACKGROUND: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs) in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents. Here we demonstrate that a high incidence of (Q63R) but not (H316Y) polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.

Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain.

Two well-characterized cannabinoid receptors (CBrs), CB1 and CB2, mediate the effects of cannabinoids and marijuana use, with functional evidence for other CBrs. CB1 receptors are expressed primarily in brain and peripheral tissues. For over a decade several laboratories were unable to detect CB2 receptors in brain and were known to be intensely expressed in peripheral and immune tissues and have traditionally been referred to as peripheral CB2 CBrs. We have reported the discovery and functional presence of CB2 cannabinoid receptors in mammalian brain that may be involved in depression and drug abuse and this was supported by reports of identification of neuronal CB2 receptors that are involved in emesis. We used RT-PCR, immunoblotting, hippocampal cultures, immunohistochemistry, transmission electron microscopy, and stereotaxic techniques with behavioral assays to determine the functional expression of CB2 CBrs in rat brain and mice brain exposed to chronic mild stress (CMS) or those treated with abused drugs. RT-PCR analyses supported the expression of brain CB2 receptor transcripts at levels much lower than those of CB1 receptors. In situ hybridization revealed CB2 mRNA in cerebellar neurons of wild-type but not of CB2 knockout mice. Abundant CB2 receptor immunoreactivity (iCB2) in neuronal and glial processes was detected in brain and CB2 expression was detected in neuron-specific enolase (NSE) positive hippocampal cell cultures. The effect of direct CB2 antisense oligonucleotide injection into the brain and treatment with JWH015 in motor function and plus-maze tests also demonstrated the functional presence of CB2 cannabinoid receptors in the central nervous system (CNS). Thus, contrary to the prevailing view that CB2 CBrs are restricted to peripheral tissues and predominantly in immune cells, we demonstrated that CB2 CBrs and their gene transcripts are widely distributed in the brain. This multifocal expression of CB2 immunoreactivity in brain suggests that CB2 receptors may play broader roles in the brain than previously anticipated and may be exploited as new targets in the treatment of depression and substance abuse.