Cannabinoid withdrawal syndrome is reduced in pre-proenkephalin knock-out mice

The functional interactions between the endogenous cannabinoid and opioid systems were evaluated in pre-proenkephalin-deficient mice. Antinociception induced in the tail-immersion test by acute Delta9-tetrahydrocannabinol was reduced in mutant mice, whereas no difference between genotypes was observed in the effects induced on body temperature, locomotion, or ring catalepsy. During a chronic treatment with Delta9-tetrahydrocannabinol, the development of tolerance to the analgesic responses induced by this compound was slower in mice lacking enkephalin. In addition, cannabinoid withdrawal syndrome, precipitated in Delta9-tetrahydrocannabinol-dependent mice by the injection of SR141716A, was significantly attenuated in mutant mice. These results indicate that the endogenous enkephalinergic system is involved in the antinociceptive responses of Delta9-tetrahydrocannabinol and participates in the expression of cannabinoid abstinence.

CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors

Interaction between brain endocannabinoid (EC) and serotonin (5-HT) systems was investigated by examining 5-HT-dependent behavioural and biochemical responses in CB1 receptor knockout mice. CB1 knockout animals exhibited a significant reduction in the induction of head twitches and paw tremor by the 5-HT2A receptor selective agonist ()DOI, as well as a reduced hypothermic response following administration of the 5-HT1A receptor agonist (±)-8-OH-DPAT. Additionally, exposure to the tail suspension test induced enhanced despair responses in CB1 knockout mice. However, the tricyclic antidepressant imipramine and the 5-HT selective reuptake inhibitor fluoxetine induced similar decreases in the time of immobility in the tail suspension test in CB1 receptor knockout and wild-type mice. No differences were found between both genotypes with regard to 5-HT2A receptor and 5-HT1A receptors levels, measured by autoradiography in different brain areas. However, a significant decrease in the ability of the 5-HT1A receptor agonist (±)-8-OH-DPAT to stimulate 35SGTPS binding was detected in the hippocampal CA1 area of CB1 receptor knockout mice. This study provides evidence that CB1 receptors are involved in the regulation of serotonergic responses mediated by 5-HT2A and 5-HT1A receptors, and suggests that a reduced coupling of 5-HT1A receptors to Gi/o proteins in the hippocampus might be involved in these effects.

BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice

Stress can cause damage and atrophy of neurons in the hippocampus by deregulating the expression of neurotrophic factors that promote neuronal plasticity. The endocannabinoid system represents a physiological substrate involved in neuroprotection at both cellular and emotional levels. The lack of CB1 receptor alters neuronal plasticity and originates an anxiety-like phenotype in mice. In the present study, CB1 knockout mice exhibited an augmented response to stress revealed by the increased despair behavior and corticosterone levels showed in the tail suspension test and decreased brain derived neurotrophic factor (BDNF) levels in the hippocampus. Interestingly, local administration of BDNF in the hippocampus reversed the increased despair behavior of CB1 knockout mice, confirming the crucial role played by BDNF on the emotional impairment of these mutants. The neurotrophic deficiency seems to be specific for BDNF since no differences were found in the levels of NGF and NT-3, two additional neurotrophic factors. Moreover, BDNF impairment is not related to the activity of its specific receptor TrkB or the activity of the transcription factor CREB. These results suggest that the lack of CB1 receptor originates an enhanced response to stress and neuronal plasticity by decreasing BDNF levels in the hippocampus that lead to impairment in the responses to emotional disturbances.

Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in mu-opioid receptor knock-out mice

The involvement of μ-opioid receptors in different behavioral responses elicited by nicotine was explored by using μ-opioid receptor knock-out mice. The acute antinociceptive responses induced by nicotine in the tail-immersion and hot-plate tests were reduced in the mutant mice, whereas no difference between genotypes was observed in the locomotor responses. The rewarding effects induced by nicotine were then investigated using the conditioning place-preference paradigm. Nicotine produced rewarding responses in wild-type mice but failed to produce place preference in knock-out mice, indicating the inability of this drug to induce rewarding effects in the absence of μ-opioid receptors. Finally, the somatic expression of the nicotine withdrawal syndrome, precipitated in dependent mice by the injection of mecamylamine, was evaluated. Nicotine withdrawal was significantly attenuated in knock-out mutants when compared with wild-type mice. In summary, the present results show that μ-opioid receptors are involved in the rewarding responses induced by nicotine and participate in its antinociceptive responses and the expression of nicotine physical dependence.

Activity of the δ-Opioid Receptor Is Partially Reduced, Whereas Activity of the κ-Receptor Is Maintained in Mice Lacking the μ-Receptor

Previous pharmacological studies have indicated the possible existence of functional interactions between μ-, δ- and κ-opioid receptors in the CNS. We have investigated this issue using a genetic approach. Here we describe in vitro and in vivo functional activity of δ- and κ-opioid receptors in mice lacking the μ-opioid receptor (MOR). Measurements of agonist-induced [35S]GTPγS binding and adenylyl cyclase inhibition showed that functional coupling of δ- and κ-receptors to G-proteins is preserved in the brain of mutant mice. In the mouse vas deferens bioassay, deltorphin II and cyclic[d-penicillamine2,d-penicillamine5] enkephalin exhibited similar potency to inhibit smooth muscle contraction in both wild-type and MOR −/− mice. δ-Analgesia induced by deltorphin II was slightly diminished in mutant mice, when the tail flick test was used. Deltorphin II strongly reduced the respiratory frequency in wild-type mice but not in MOR −/− mice. Analgesic and respiratory responses produced by the selective κ-agonist U-50,488H were unchanged in MOR-deficient mice. In conclusion, the preservation of δ- and κ-receptor signaling properties in mice lacking μ-receptors provides no evidence for opioid receptor cross-talk at the cellular level. Intact antinociceptive and respiratory responses to the κ-agonist further suggest that the κ-receptor mainly acts independently from the μ-receptor in vivo. Reduced δ-analgesia and the absence of δ-respiratory depression in MOR-deficient mice together indicate that functional interactions may take place between μ-receptors and central δ-receptors in specific neuronal pathways.

Nicotine-induced antinociception, rewarding effects and physical dependence are decreased in mice lacking the preproenkephalin gene

It has been shown previously that the endogenous opioid system may be involved in the behavioral effects of nicotine. In the present study, the participation of endogenous enkephalins on nicotine responses has been investigated by using preproenkephalin knock-out mice. Acute nicotine-induced hypolocomotion remained unaffected in these mice. In contrast, antinociception elicited in the tail-immersion and hot-plate tests by acute nicotine administration was reduced in mutant animals. The rewarding properties of nicotine were then investigated using the place-conditioning paradigm. Nicotine induced a conditioned place preference in wild-type animals, but this effect was absent in knock-out mice. Accordingly, in vivo microdialysis studies revealed that the enhancement in dopamine extracellular levels in the nucleus accumbens induced by nicotine was also reduced in preproenkephalin-deficient mice. Finally, the somatic expression of the nicotine withdrawal syndrome precipitated in nicotine-dependent mice by mecamylamine was significantly attenuated in mutant animals. In summary, the present results indicate that endogenous opioid peptides derived from preproenkephalin are involved in the antinociceptive and rewarding properties of nicotine and participate in the expression of physical nicotine dependence.

A topological proof that surface relators are test words

Vegeu el resum a l'inici del document del fitxer adjunt.

The black-white test score gap widens with age?

We re-examine the theoretical concept of a production function for cognitive achievement, and argue that an indirect production function that depends upon the variables that constrain parents' choices is both moretractable from an econometric point of view, and more interesting from an economic point of view than is a direct production function that depends upon a detailed list of direct inputs such as number of books in the household. We estimate flexible econometric models of indirect production functions for two achievement measures from the Woodcock-Johnson Revised battery, using data from two waves of the Child Development Supplement to the PSID. Elasticities of achievement measures with respect to family income and parents' educational levels are positive and significant. Gaps between scores of black and white children narrow or remain constant as children grow older, a result that differs from previous findings in the literature. The elasticities of achievement scores with respect to family income are substantially higher for children of black families, and there are some notable difference in elasticities with respect to parents' educational levels across blacks and whites.

Resultados del test de consumidores de manzana del proyecto ISAFRUIT

El IRTA ha coordinado el desarrollo de un test de consumidores de nuevas variedades de manzana que se ha desarrollado dentro el programa de trabajo denominado ‘Implementación de nuevas variedades de manzana en base a las preferencias de los consumidores’ en el marco del proyecto europeo de investigación ISAFRUIT. En este programa de trabajo han participado 14 instituciones de investigación, universidades y empresas de Europa

Markup Test Reader: eina de creació i lectura de formularis de test

El projecte exposat en aquestes pàgines és un document d'estudi, anàlisi, disseny, programació i procés de proves en la confecció d'una aplicació de creació i lectura de formularis de test. Aquesta aplicació parteix de les possibilitats de millora de les prestacions, usabilitat i escalabilitat que poden oferir les tècniques de visió en computador en aquest camp. El projecte s'ha basat en un exemple en concret per tal d'oferir una eina vàlida per a la automatització de les tasques que en una empresa de recursos humans es poden donar a l'hora de gestionar la informació dels test psicotècnics que necessiten gestionar. El projecte parteix d'unes premisses bàsiques tals com: l'ús de tècniques en visió per computador, la modularitat, el compliment d'estàndards, la facilitat d'ús i la facilitat en la gestió de canvis.

Diseño de una plataforma de lectura, test y caracterización para ROICs de rayos X basada en el microprocesador LEON

Aquest project es situa dins del marc del CNM-IMB (CSIC). Consisteix en el disseny d'un sistema de biòpsia mamaria en temps real. Per realitzar aquest sistema s’ha dissenyat una plataforma de lectura, test y caracterització pel ROIC Medipix2 que es basa en el microprocessador LEON3 i és programat sobre una FPGA.

Fear assessment in pigs exposed to a novel object test

The experiment aimed to study approach and locomotive behaviour as indicators of fear in a novel object test carried out in pigs. Thirty post-weaning (30 kg) and 30 finishing (90 kg) pigs were exposed to visual, auditory and olfactory novel stimuli during 2 different experiments. The facilities consisted of a test pen in which a trough was located. The trough contained chopped apples. Once the animals were trained to enter the test pen individually they were subjected to 3 different fear stimuli. These stimuli were applied in the test pen and next to the trough. The variables studied were feeding behaviour, approach behaviour (the distance and position of the animal with respect to the trough) and locomotive behaviour (general activity, reluctance to move, turning back and retreat attempts). Two groups were studied: saline and midazolam treated group. Twenty minutes before the start of the sessions, 15 post-weaning and finishing pigs received an intramuscular injection of 0.20 and 0.15 mg/kg, respectively, midazolam (Dormicum1). The saline pigs (15 animals per group) were injected with saline. The administration of midazolam increased the feeding behaviour and approaching behaviour, and reduced the locomotive behaviour. In front of the visual and olfactory stimuli post-weaning pigs showed a higher general activity than finishing pigs, but the contrary was found when the auditory stimulus was applied. The olfactory stimulus was more related to the turning back behaviour, whereas the visual stimulus was more related to retreat attempts. Although it could be concluded that reluctant to move was the most common response to the different fear stimuli applied in our study regardless of the age of animals, the combination of reluctant to move and turning back would be a good criterion to assess fear in domestic pigs. The use of midazolam as anxiolytic for studies of fear in commercial conditions in pigs is recommended.

Is real GDP stationary? Evidence from a panel unit root test with cross-sectional dependence and historical data

We use historical data that cover more than one century on real GDP for industrial countries and employ the Pesaran panel unit root test that allows for cross-sectional dependence to test for a unit root on real GDP. We find strong evidence against the unit root null. Our results are robust to the chosen group of countries and the sample period. Key words: real GDP stationarity, cross-sectional dependence, CIPS test. JEL Classification: C23, E32

Test de sobrecarga acuosa y manometría de alta resolución para valoración de la resistencia al flujo esófago-gástrico en paciente s con acalasia

La manometría convencional es el “gold standard” para diagnosticar trastornos motores del esófago, pero la información que da sobre la repercusión funcional de estas alteraciones es escasa. La manometría de alta resolución permite estudiar con detalle la motilidad esofagogástrica mediante la generación de mapas topográficos de presiones desde la orofaringe hasta el estómago. Hipótesis: Si la generación de mapas topográficos de presiones en el esófago mediante manometría de alta resolución demuestra la resistencia al flujo esofagogástrico. Objetivo: Comprobar si un test con sobrecarga de agua puede mostrar la presencia de resistencia al flujo esofagogástrico en pacientes con acalasia. Método: Estudiamos 2 grupos de pacientes con alteración de la motilidad esofágica. Un grupo de 8 pacientes que cumplen criterios manométricos de acalasia y, como grupo control, 8 pacientes con disfunción del peristaltismo esofágico ( DPE). A cada paciente se le realizó un test de sobrecarga que consistía en la ingesta rápida de 200 ml de agua mientras se registraban las presiones esofágicas. Resultados: Los pacientes con acalasia ingirieron el agua más lentamente que los pacientes con DPE (82± 14 seg vs 34± 6 seg, p&0,05). Mientras la unión gastroesofágica (UGE) permaneció contraída en el grupo de pacientes con acalasia (46,6± 6 mm Hg; p&0,05), permaneció relajada durante el tiempo del ingesta en pacientes con DPE ( 16,6 ± 4,7 mm Hg). La unión esófago-gástrica (UGE) experimentó una migración proximal en pacientes con acalasia de 1,3 ± 0 cm mientras que en el grupo control no migró (0 cm; p&0,05). La ingesta de agua se asoció a un incremento de la presión del esófago distal (2 cm por encima de la UGE) significativamente mayor en los pacientes con acalasia que en los pacientes con DPE (42,2 ± 20 vs 9,5± 7,9 mm Hg respectivamente, p&0,05) lo que produjo un incremento del gradiente de presión esófago-gástrico en pacientes con acalasia (16± 0,9 mmHg) que no se observó en los pacientes con DPE (0,1 ± 0,4 mmHg ; p&0,05). Conclusión: Un test con sobrecarga de agua durante la medición de la topografía y de las presiones esofágicas demuestra obstrucción al flujo esofagogástrico en los pacientes con acalasia. Este test podría contribuir a valorar la repercusión funcional en pacientes con acalasia y podría servir para el seguimiento de pacientes con acalasia tratados.

Metodologia d'avaluació i disseny d'un test d'usuari aplicat a la web de l'institut català de la salut

La finalitat d'aquest projecte consisteix a establir una metodologia d'avaluació i disseny d'un test d'usuari. Es vol no només avaluar un lloc web en concret, sinó també establir una sèrie de pautes que es puguin aplicar a qualsevol altra aplicació futura.