Dextromethorphan attenuated the higher vulnerability to inflammatory thermal hyperalgesia caused by prenatal morphine exposure in rat offspring

<p>Abstract</p> <p>Background</p> <p>Co-administration of dextromethorphan (DM) with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on inflammatory hyperalgesia in morphine-exposed offspring. Therefore, we attempt to investigate the possible effect of prenatal morphine exposure on the vulnerability to hyperalgesia and the possible therapeutic effect of DM in the present study.</p> <p>Methods</p> <p>Fifty μl of carrageenan (20 mg/ml) was injected subcutaneously into the plantar surface of the right hind paw in p18 rats to induce hyperalgesia. Mean paw withdrawal latency was measured in the plantar test to index the severity of hyperalgesia. Using Western blotting and RT-PCR, the quantitative analyses of NMDA receptor NR1 and NR2B subunits were performed in spinal cords from different groups of animals.</p> <p>Results</p> <p>In the carrageenan-induced hyperalgesia model, rat offspring passively exposed to morphine developed a severe hyperalgesia on postnatal day 18 (p18), which also had a more rapid time course than those in the controls. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Western blot and RT-PCR analysis showed that the levels of protein and mRNA of NMDA receptor NR1 and NR2B subunits were significantly higher in the lumbar spinal cords of rats (p14) exposed to prenatal morphine; the co-administration of DM could reverse the effect of morphine on NR1 and attenuate the effect on NR2B.</p> <p>Conclusions</p> <p>Thus, DM may have a great potential in the prevention of higher vulnerability to inflammatory thermal hyperalgesia in the offspring of morphine-addicted mothers.</p

Attenuation by dextromethorphan on the higher liability to morphine-induced reward, caused by prenatal exposure of morphine in rat offspring

Co-administration of dextromethorphan (DM) with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on morphine-induced reward and behavioral sensitization (possibly related to the potential to induce morphine addiction) in morphine-exposed offspring. Conditioned place preference and locomotor activity tests revealed that the p60 male offspring of chronic morphine-treated female rats were more vulnerable to morphine-induced reward and behavioral sensitization. The administration of a low dose of morphine (1 mg/kg, i.p.) in these male offspring also increased the dopamine and serotonin turnover rates in the nucleus accumbens, which implied that they were more sensitive to morphine. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Thus, DM may possibly have a great potential in the prevention of higher vulnerability to psychological dependence of morphine in the offspring of morphine-addicted mothers

Asic3−/− Female Mice with Hearing Deficit Affects Social Development of Pups

BACKGROUND: Infant crying is an important cue for mothers to respond adequately. Inappropriate response to infant crying can hinder social development in infants. In rodents, the pup-mother interaction largely depends on pup's calls. Mouse pups emit high frequency to ultrasonic vocalization (2-90 kHz) to communicate with their dam for maternal care. However, little is known about how the maternal response to infant crying or pup calls affects social development over the long term. METHODOLOGY/PRINCIPAL FINDINGS: Here we used mice lacking acid-sensing ion channel 3 (Asic3(-/-)) to create a hearing deficit to probe the effect of caregiver hearing on maternal care and adolescent social development. Female Asic3(-/-) mice showed elevated hearing thresholds for low to ultrasonic frequency (4-32 kHz) on auditory brain stem response, which thus hindered their response to their pups' wriggling calls and ultrasonic vocalization, as well as their retrieval of pups. In adolescence, pups reared by Asic3(-/-) mice showed a social deficit in juvenile social behaviors as compared with those reared by wild-type or heterozygous dams. The social-deficit phenotype in juvenile mice reared by Asic3(-/-) mice was associated with the reduced serotonin transmission of the brain. However, Asic3(-/-) pups cross-fostered to wild-type dams showed rescued social deficit. CONCLUSIONS/SIGNIFICANCE: Inadequate response to pups' calls as a result of ASIC3-dependent hearing loss confers maternal deficits in caregivers and social development deficits in their young

A human gene encoding morphine modulating peptides related to NPFF and FMRFamide

AbstractFMRFamide-related peptides have been isolated from both invertebrates and vertebrates and exhibit a wide range of biological effects in rats. We show here that in humans 2 FMRFamide-related peptides are encoded by a single gene expressed as a spliced mRNA. The larger predicted peptide (AGEGLNSQFWSLAAPQRFamide) differs from the peptide isolated from bovines (AGEGLSSPFWSLAAPQRFamide) by the substitutions of 2 amino acids. The shorter predicted peptide (NPSF, SQAFLFQPQRFamide) is 3 amino acids longer than the bovine 8 amino-acid NPFF (FLFQPQRFamide) or the human NPFF peptide isolated from serum [5], suggesting that the encoded protein is subject to cleavage by a tripeptidyl peptidase or by a novel processing mechanism. On rat spinal cord, the larger peptide is indistinguishable in activity from the equivalent bovine peptide whereas the smaller extended peptide is inactive

MAPEANDO A PRODUÇÃO SOBRE O LIVRO DIDÁTICO DE SOCIOLOGIA: UM ESTADO DA ARTE NO CAMPO ACADÊMICO BRASILEIRO

TCC (graduação) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas, Curso de Ciências Sociais.Este Trabalho de Conclusão de Curso tem como objetivo central realizar o “estado da arte” do livro didático de sociologia. Foi realizado o mapeamento de teses e dissertações produzidas em programas de pós-graduação stricto sensu, localizando-se 30 trabalhos entre os anos de 1996-2017, que se debruçaram na análise de livros didáticos destinados ao ensino de sociologia, direta ou indiretamente. A temática foi destacada por se compreender que o livro didático participa do processo de rotinização da sociologia no Brasil, mesmo nos períodos em que a disciplina não constou como obrigatória nos currículos oficiais nacionais, contribuindo também para a produção no subcampo do ensino de sociologia. Tendo como norte a teoria do campo de Bourdieu e amparo na literatura a respeito do ensino de sociologia, percorreu-se no primeiro capítulo a trajetória da sociologia na escola por meio da sua relação com o livro didático, e, no segundo capítulo, localizou-se o campo do ensino de sociologia através das pesquisas que se dedicaram ao estado da arte. Com base na metodologia qualitativa e quantitativa, apresentou-se no terceiro capítulos a análise dos trabalhos selecionados neste estado da arte. Como resultados, em termos gerais, pode-se afirmar que as pesquisas sobre o livro didático têm tido maior amparo no campo científico das ciências sociais, bem como têm sido alavancadas mais recentemente pelo mestrado profissional. Além disso, pode-se verificar que os livros didáticos participam das narrativas sobre a trajetória do ensino de sociologia, percorrendo longos períodos que abraçam desde o início do século XX até o mais atual, seja por meio de pesquisas históricas ou daquelas que envolvem o currículo. Por fim, indica-se que o Programa Nacional do Livro Didático tem impactado nas pesquisas acerca do livro didático, sendo aqueles livros didáticos aprovados pelo programa os mais investigados.This work aims to make a state of the art of Sociology textbooks. A mapping of dissertations and thesis of stricto sensu postgraduate studies have been made, totalizing 30 works between the years of 1996 to 2007, which have analyzed Sociology textbooks directly or indirectly. This theme has been chosen because textbooks participate of a routinization process of Sociology in Brazil, even when the discipline wasn't mandatory in official national curricula, contributing also to the production of the subfield of Sociology study. Guiding by Bourdieu's field theory and having support in literature concerning the Sociology study, the first chapter went through the path of Sociology in school as a relationship of itself with the textbook, and the second chapter have located the Sociology field through researches dedicated to the state of the art. Using both qualitative and quantitative methodologies, the third chapter shows an analysis of selected works. As a result, it can be affirmed that textbook's researches have greater support at the scientific field of Social Sciences, just as they have been leveraged more recently in the master's degree. Besides, it can be checked that textbooks participate of the narratives of Sociology study's path, traveling a long way from the 20th century until today, either by historical researches, as by the curricula's one. Lastly, it's shown that Programa Nacional do Livro Didático has impacted textbooks' researches; being the books approved by the program the most investigated ones

The Effect of ASIC3 Knockout on Corticostriatal Circuit and Mouse Self-grooming Behavior

Stereotypic and/or repetitive behavior is one of the major symptoms of autism spectrum disorder (ASD). Increase of self-grooming behavior is a behavioral phenotype commonly observed in the mouse models for ASD. Previously, we have shown that knockout of acid-sensing ion channel 3 (ASIC3) led to the increased self-grooming behavior in resident-intruder test. Given the facts that ASIC3 is mainly expressed in the peripheral dorsal root ganglion (DRG) and conditional knockout of ASIC3 in the proprioceptors induced proprioception deficits. We speculate a hypothesis that stereotypic phenotype related to ASD, pararalled with striatal dysfunction, might be caused by proprioception defect in the peripheral sensory neuron origin. Herein, we investigate in depth whether and how ASIC3 is involved in the regulation of self-grooming behavior. First, we observed that Asic3 null mutant mice exhibited increased self-grooming in social interaction during juvenile stage. Similarly, they displayed increased self-grooming behavior in a novel cage in the absence of cagemate. To further understand the mechanism by which ASIC3 affects grooming behavior, we analyzed neurochemical, neuropathological and electrophysiological features in the dorsal striatum of Asic3 null mutant mice. Knockout of Asic3 increased dopamine (DA) activity and phospho-ERK immunoreactivities in the dorsal striatum. Furthermore, we detected a lower paired-pulse ratio (PPR) and impaired long-term potentiation (LTP) in corticostriatal circuits in Asic3 null mutant mice as compared with wild-type (WT) littermates. Moreover, knockout of Asic3 altered the medial spiny neurons in the striatum with defects in presynaptic function and decrease of dendritic spines. Lastly, genetic ablation of Asic3 specifically in parvalbumin-positive (PV+) cells resulted in the increase of self-grooming behavior in mice. These findings suggest knockout of Asic3 in the PV+ neurons alters grooming behavior by co-opting corticostriatal circuits