Living frisbees: riesgos de patologías mentales en niños y niñas expuestos a thc durante su gestación / Living frisbees: risks of mental pathologies in boys and girls exposed to thc during their pregnancy

La Cannabis sativa es una planta que contiene componentes psicoactivos (principalmente tetrahidrocannabinol) y actualmente corresponde a la droga ilícita más consumida a nivel mundial. Además, desde el área de la salud mental, ha habido un creciente interés en evaluar la relación entre el consumo de marihuana y el desarrollo de trastornos mentales. En este contexto, considerando tanto este creciente aumento en su consumo a nivel mundial y el interés por conocer si está involucrada en la patogénesis de patologías de la esfera psiquiátrica, es clave analizar qué posibles riesgos de desarrollar patologías mentales presentan aquellos niños expuestos al tetrahidrocannabinol durante la gestación. A partir de esta situación, el objetivo de este FRISBEEs es determinar si los niños/as expuestos a THC durante su gestación tienen un mayor riesgo de patologías mentales, en comparación a aquellos niños no expuestos durante su gestación. Los materiales y métodos utilizados para responder esta pregunta fueron obtenidos a partir de una búsqueda bibliográfica en dos bases de datos, donde se analizó la evidencia disponible, y se seleccionó el estudio primario titulado "Maternal tobacco, cannabis and alcohol use during pregnancy and risk of adolescent psychotic symptoms in offspring", ya que era el que más se aproximaba a poder responder nuestra pregunta clínica. Este se analizó de forma crítica, llegando al resultado de que el estudio no fue concluyente en establecer una asociación entre el uso de cannabis y síntomas psicóticos. Como conclusión, dado que no se pudo llegar a establecer una asociación entre el uso de cannabis y el desarrollo de patologías mentales, se debería realizar más investigación sobre el tema dado la magnitud del consumo de cannabis a nivel mundial, para así poder llegar a conclusiones clínicas basadas en la evidencia y poder dar recomendaciones clínicas a las pacientes embarazadas.

Cannabis sativa is a plant that contains psychoactive components (mainly tetrahydrocannabinol) and currently corresponds to the most widely consumed illicit drug worldwide. In addition, from the area of mental health, there has been a growing interest in evaluating the relationship between marijuana use and the development of mental disorders. In this context, considering both this growing increase in its consumption worldwide and the interest in knowing if it is involved in the pathogenesis of pathologies in the psychiatric sphere, it is essential to analyze what possible risks of developing mental pathologies present those children exposed to tetrahydrocannabinol during gestation. Based on this situation, the objective of this FRISBEEs is to determine whether children exposed to THC during their pregnancy have a greater risk of mental pathologies, compared to those children not exposed during their pregnancy. The materials and methods used to answer this question were obtained from a bibliographic search in two databases, where the available evidence was analyzed, and the primary study entitled "Maternal tobacco, cannabis and alcohol use during pregnancy and risk of adolescent psychotic symptoms in offspring ", as he was the closest to answering our clinical question. This was critically analyzed, reaching the result that the study was not conclusive in establishing an association between the use of cannabis and psychotic symptoms. In conclusion, given that it was not possible to establish an association between the use of cannabis and the development of mental pathologies, more research should be carried out on the subject given the magnitude of cannabis use worldwide, in order to reach conclusions. evidence-based clinics and to be able to give clinical recommendations to pregnant patients

Alcohol consumption during pregnancy and perinatal results: a cohort study / Consumo de álcool durante a gravidez e resultados perinatais: um estudo de coorte

ABSTRACT CONTEXT AND OBJECTIVE: Alcohol consumption during pregnancy is a significant social problem that may be associated with adverse perinatal outcomes. The aim of this study was to describe alcohol consumption during pregnancy and to study its association with low birth weight, newborns small for gestational age and preterm birth. DESIGN AND SETTING: Nested cohort study, in the city of Ribeirão Preto, São Paulo, Brazil. METHODS: 1,370 women and their newborns were evaluated. A standardized questionnaire on health and lifestyle habits was applied to the mothers. Anthropometry was performed on the newborns. Alcohol consumption was defined as low, moderate or high, as defined by the World Health Organization. Adjusted logistic regression analysis was used. RESULTS: 23% of the women consumed alcohol during pregnancy. Consumption mainly occurred in the first trimester (14.8%) and decreased as the pregnancy progressed. The median alcohol intake was 3.89 g (interquartile range, IQR = 8 g) per day. In the unadjusted analysis, alcohol consumption increased the risk of low birth weight almost twofold (odds ratio, OR 1.91; 95% confidence interval, CI: 1.25-2.92). The risk was lower in the adjusted analysis (OR 1.62; 95% CI: 1.03-2.54). Alcohol consumption did not show associations with small for gestational age or preterm birth. There was greater risk of low birth weight and newborns small for gestational age and preterm birth among mothers who were both smokers and drinkers. CONCLUSIONS: The alcohol consumption rate during pregnancy was 23% and was independently associated with low birth weight, but there was no risk of newborns small for gestational age or preterm birth.

RESUMO CONTEXTO E OBJETIVO: O consumo de álcool durante a gravidez é um problema social significativo que pode estar associado a resultados perinatais adversos. O objetivo deste estudo foi descrever o consumo de álcool na gestação e avaliar sua associação com recém-nascido de baixo peso, pequeno para idade gestacional e pré-termo. TIPO DE ESTUDO E LOCAL: Estudo de coorte aninhado, na cidade de Ribeirão Preto, São Paulo, Brasil. Foram avaliadas 1.370 mulheres e seus recém-nascidos. Foi aplicado às mães um questionário padronizado sobre saúde e hábitos de vida. Antropometria foi realizada nos recém-nascidos. MÉTODOS:Consumo de álcool foi definido como baixo, moderado e elevado segundo a Organização Mundial de Saúde. Foi utilizada análise de regressão logística ajustada. RESULTADOS: 23% das gestantes consumiram álcool durante a gravidez. A maior parte do consumo ocorreu no primeiro trimestre (14,8%) e diminuiu conforme progredia a gravidez. A mediana de ingestão de álcool foi de 3,89 g (interval interquartil, IIQ = 8 g) por dia. Na análise não ajustada, o consumo de álcool aumentou em quase duas vezes (odds ratio , OR 1,91, intervalo de confiança, IC 95%; 1,25-2,92) o risco de baixo peso, que se reduziu após ajuste (OR 1,62; IC 95%; 1,03-2,54). Não houve associação entre consumo de álcool e pequeno para idade gestacional ou pré-termo. Observou-se maior risco de baixo peso, neonato pequeno para idade gestacional e pré-termo em gestantes simultaneamente fumadoras e bebedoras. CONCLUSÕES: O consumo de álcool na gestação foi de 23% e esteve associado independentemente com o baixo peso ao nascer, mas não houve risco para neonato pequeno para idade gestacional e pré-termo.

Toxicodependência e maternidade: uma revisão de literatura / Drug addiction and maternity: a literature review / Drogodependencia y maternidad: una revisión de literatura

Pretende fazer-se uma revisão da literatura acerca da parentalidade de mães toxicodependentes, abordando as 1) consequências da toxicodependência na maternidade e 2) as condições ambientais e contextuais dos pais toxicodependentes, e suas famílias de origem. A literatura atual aponta para um comportamento parental perturbado das mães toxicodependentes, embora saliente a importância da gravidez e maternidade como fator predisponente ao início de um tratamento e recuperação. São referidos efeitos disruptivos na saúde, nascimento e desenvolvimento pós-natal das crianças, na qualidade do vínculo e da interação mãe-filho, bem como repercussões que se refletem na inadequação de cuidados maternais e risco aumentado de negligência e abuso. A investigação focaliza a atenção em algumas áreas específicas do comportamento parental, verificando-se lacunas e resultados nem sempre consistentes, falta de estudos contemplando a relação direta entre abuso de substâncias e disfunções familiares e da parentalidade, bem como a experiência e dificuldades inerentes à parentalidade nesta situação de risco. É feita uma análise da investigação atual e fornecidas algumas diretrizes para futuras investigações.

This article is a literature review on parenting of drug addicted mothers, addressing 1) the consequences of drug abuse in maternity and 2) the environmental conditions of drug addicted parents, and their families of origin. The current literature points to a disturbed parental behaviour of drug addicted mothers, although it stresses the importance of pregnancy and maternity as a predisposing factor to the beginning of a recovery treatment. Authors refer disruptive effects on health, birth and post-natal children development, on attachment quality and on mother-child interaction, as well as inadequate maternal care and high risk of abuse and negligence. The research focuses attention on specific areas of parental behavior, in which we can find gaps and incoeherences, characterized by the lack of studies covering the direct link between substance abuse and family dysfunction and parenting, as well as the experience and difficulties of parenting in the situation of risk that is drug addiction. We make an analysis of the current investigation and suggest some guidelines for future research.

El objetivo de la investigación es elaborar una revisión de la literatura sobre la parentalidad de las madres drogodependientes abordando las 1) consecuencias de la drogodependencia en la maternidad y 2) las condiciones ambientales y contextuales de los padres drogodependientes, y sus familias de origen. La literatura actual se orienta hacia un comportamiento parental perturbado de las madres drogodependientes, aunque realce la importancia del embarazo y maternidad como factor predisponente al inicio de un tratamiento y recuperación. Se refieren efectos disruptivos en la salud, nacimiento y desarrollo de los recién nacidos en el puerperio, en la calidad del vínculo e interacción madre-hijo, así como repercusiones que se reflejan en la inadecuación de los cuidados maternales y riesgo incrementado de negligencia y abuso. La investigación se focaliza en algunas áreas específicas del comportamiento parental, verificándose fallos y resultados que no son siempre consistentes, falta de estudios que reflejen la relación directa entre el abuso de substancias y disfunciones familiares y de la parentalidad, así como la experiencia y dificultades inherentes a la parentalidad en esta situación de riesgo. Se hace un análisis de la investigación actual y se facilitan algunas directrices para futuras investigaciones.

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of kappa group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid ...

Morphine infusions into the rostrolateral periaqueductal gray affect maternal behaviors

It is well established that morphine inhibits maternal behaviors. Previous studies by our group have shown activation of the rostrolateral periaqueductal gray (rlPAG) upon inhibition-intended subcutaneous injections of morphine. In this context, we demonstrated that a single naloxone infusion into the rlPAG, following this opioid-induced inhibition, reactivated maternal behaviors. Since these data were obtained by using peripheral morphine injections, the present study was designed to test whether morphine injected directly into the rlPAG would affect maternal behaviors. Our hypothesis that morphine acting through the rlPAG would disrupt maternal behaviors was confirmed with a local infusion of morphine. The mothers showed shorter latency for locomotor behavior to explore the home cage (P = 0.049). Inhibition was especially evident regarding retrieving (P = 0.002), nest building (P = 0.05) and full maternal behavior (P = 0.023). These results support the view that opioidergic transmission plays a behaviorally meaningful inhibitory role in the rostrolateral PAG.

Intra uterine growth retardation in rats treated with essential oil of rosmarinus officinalis linn

The essential oil of Rosmarinus officinalis L. (EORO) is used in cosmetics, in the food industry and in medicines, presenting antimicrobial and antifungal activity. Aim of the study: to observe maternal toxicity and embryo development after treatment of dams with EORO. Inseminated rats were distributed in four groups (n =15): Control (C) (saline 0.5ml) and treated with 242 (T1), 484 (T2) and 968mg/Kg (T3) of EORO, from the fifth to the seventh dpc and sacrificed on the 15th dpc. Variables analyzed: maternal behavior, body weight gain, food consumption, kidneys, liver and ovaries weight, hemogram, number of corpora lutea, implants, live, dead, malformed fetuses and placenta and fetuses weight. Statistics: Dunnett and Chi-square tests (α=0.05). The EORO higher dose reduced (p<0.05) maternal number of erythrocytes; the haematocrit, hemoglobin concentration and the fetuses body weight. Conclusions: Highest dose of EORO reduce the fetuse´s body weight and induced anemia in the dams.

Proliferação, apoptose e histomorfometria da glândula mamária de ratas tratadas com tiroxina na lactação e ao desmame e desenvolvimento dos filhotes / Proliferation, apoptosis and mammary gland histomorphometry of thyroxine-treated rats on lactation and after weaning and development of offspring

O objetivo deste estudo foi avaliar a histomorfometria e a taxa de proliferação e apoptose da glândula mamária de ratas tratadas com tiroxina pela imuno-expressão de CDC-47 e caspase-3, respectivamente. Também foi avaliado o desenvolvimento dos filhotes de ratas tratadas com tiroxina. Foram utilizadas 36 ratas distribuídas em dois grupos, tratado com tiroxina e controle. Após 60 dias de tratamento com tiroxina, as ratas foram acasaladas. Seis animais/grupo foram sacrificados no 2° e 21° dias de lactação e no 5° dia após o desmame. Houve diferença significativa entre grupos apenas no quinto dia após o desmame. O tratamento com tiroxina aumentou a taxa de apoptose caracterizada pela maior expressão de caspase-3 nas células do epitélio mamário. As mães tratadas com tiroxina apresentaram comportamento alterado, mas não houve diferença significativa no que se refere aos cuidados com o filhote quanto a higienização e aquecimento. Levando-se em consideração o sexo e o tamanho da ninhada, os filhotes das ratas tratadas com tiroxina e controle não apresentaram diferença significativa de peso ao desmame. Conclui-se que a administração de baixas doses de tiroxina aumenta a taxa de apoptose, caracterizada pelo aumento da expressão de caspase-3 no epitélio mamário cinco dias após o desmame, mas não altera a taxa de proliferação celular e o comportamento materno.

The purpose of this study was to evaluate mammary gland histomorphometry and proliferation rate and apoptosis of thyroxine-treated rats by CDC-47 and caspase-3 immunoexpression. The development of thyroxine-treated rats offspring was also evaluated. Thirty-six female rats were used, distributed in two groups, treated and non-treated with thyroxine. After 60 days of treatment, with thyroxine, rats were mated. Six animals/group were sacrificed on the 2nd and 21st days of lactation and on the 5th day after weaning. A significant difference was observed between groups only on the 5th day after weaning. Thyroxine treatment increased apoptosis rate, which was characterized by a higher caspase-3 expression in mammary epithelial cells. Thyroxine-treated mothers presented changed behavior, but there was no significant difference regarding taking care of offspring, as for cleaning offspring and keeping them warm. Taking into account sex and size of offspring, those from control and thyroxine-treated mothers presented no significant difference of weight and weaning. In conclusion, administering low doses of thyroxine increases apoptosis rate, which is characterized by the increased caspase-3 immunoexpression in mammary epithelial cells 5 days after weaning. But does not affect proliferation rate and development of thyroxine-treated rats offspring.

Effect of 5-HT1B receptor agonists injected into the prefrontal cortex on maternal aggression in rats

Serotonin (5-HT1B) receptors play an essential role in the inhibition of aggressive behavior in rodents. CP-94,253, a 5-HT1B receptor agonist, can reduce aggression in male mice when administered directly into the ventro-orbitofrontal (VO) prefrontal cortex (PFC). The objective of the current study was to assess the effects of two selective 5-HT1B receptor agonists (CP-94,253 and CP-93,129), microinjected into the VO PFC, on maternal aggressive behavior after social instigation in rats. CP-94,253 (0.56 µg/0.2 µL, N = 8, and 1.0 µg/0.2 µL, N = 8) or CP-93,129 (1.0 µg/0.2 µL, N = 9) was microinjected into the VO PFC of Wistar rats on the 9th day postpartum and 15 min thereafter the aggressive behavior by the resident female against a male intruder was recorded for 10 min. The frequency and duration of aggressive and non-aggressive behaviors were analyzed using ANOVA and post hoc tests. CP-93,129 significantly decreased maternal aggression. The frequency of lateral attacks, bites and pinnings was reduced compared to control, while the non-aggressive behaviors and maternal care were largely unaffected by this treatment. CP-94,253 had no significant effects on aggressive or non-aggressive behaviors when microinjected into the same area of female rats. CP-93,129, a specific 5-HT1B receptor agonist, administered into the VO PFC reduced maternal aggressive behavior, while the CP-94,253 agonist did not significantly affect this behavior after social instigation in female rats. We conclude that only the 5-HT1B receptor agonist CP-93,129 administered into the VO PFC decreased aggression in female rats postpartum after social instigation.

The effect of 5-HT2a/2c receptor agonist microinjected into central amygdaloid nucleus and median preoptic area on maternal aggressive behavior in rats

OBJETIVO: Resultados de muitos estudos sustentam a hipótese de que a serotonina (5-HT) está relacionada com a inibição do comportamento agressivo. Foram examinados os efeitos potenciais pró e anti-agressivos do agonista de receptores 5-HT2A/2C em regiões específicas do cérebro. MÉTODO: Ratas fêmeas Wistar no sétimo dia pós-parto receberam microinjeções do agonista seletivo de receptores 5-HT2A/2C, a-methyl-5-hydroxytryptamine maleate (0,2 a 1,0 µg/0,2 µl), no núcleo central da amígdala e núcleo pré-óptico medial. Para cada área estudada, as freqüências dos comportamentos: locomoção, investigação social, postura de ameaça, ataques (frontal e lateral) e ato de morder um intruso, foram comparadas entre os diferentes tratamentos por uma análise da variância, seguida quando apropriado do teste de Tukey. RESULTADOS: Os resultados mostraram que a microinjeção do agonista seletivo a-methyl-5-hydroxytryptamine maleate no núcleo central da amígdala aumentou a agressividade materna, mas não foram encontrados efeitos estatisticamente significativos no comportamento agressivo após a microinjeção do agonista seletivo de receptores 5-HT2A/2C no núcleo pré-óptico medial nas diferentes diluições estudadas. CONCLUSÕES: Os dados atuais e prévios sobre os efeitos pró e anti-agressivos do agonista dos receptores 5-HT2a/2c quando microinjetado no núcleo pré-óptico medial, em comparação com a microinjeção no núcleo central da amígdala, no septo medial (MS) e substância cinzenta periaqueductal em ratas apontam para populações funcionalmente independentes de receptores na amígdala-septo-hipotálamo e substância cinzenta periaqueductal, que são responsáveis pelo controle do comportamento agressivo. É possível que os receptores 5-HT2a/2c da amígdala possam aumentar o comportamento agressivo das fêmeas lactantes, como resultado de mudanças decorrentes do estado emocional de medo.

Maternal aggression in Wistar rats: effect of 5-HT2A/2C receptor agonist and antagonist microinjected into the dorsal periaqueductal gray matter and medial septum

The objective of the present study was to assess the role of the 5-HT2A/2C receptor at two specific brain sites, i.e., the dorsal periaqueductal gray matter (DPAG) and the medial septal (MS) area, in maternal aggressive behavior after the microinjection of either a 5-HT2A/2C receptor agonist or antagonist. Female Wistar rats were microinjected on the 7th postpartum day with the selective agonist alpha-methyl-5-hydroxytryptamine maleate (5-HT2A/2C) or the antagonist 5-HT2A/2C, ketanserin. The agonist was injected into the DPAG at 0.2 (N = 9), 0.5 (N = 10), and 1.0 æg/0.2 æl (N = 9), and the antagonist was injected at 1.0 æg/0.2 æl (N = 9). The agonist was injected into the medial septal area (MS) at 0.2 (N = 9), 0.5 (N = 7), and 1.0 æg/0.2 æl (N = 6) and the antagonist was injected at 1.0 æg/0.2 æl (N = 5). For the control, saline was injected into the DPAG (N = 7) and the MS (N = 12). Both areas are related to aggressive behavior and contain a high density of 5-HT receptors. Non-aggressive behaviors such as horizontal locomotion (walking) and social investigation and aggressive behaviors such as lateral threat (aggressive posture), attacks (frontal and lateral), and biting the intruder were analyzed when a male intruder was placed into the female resident's cage. For each brain area studied, the frequency of the behaviors was compared among the various treatments by analysis of variance. The results showed a decrease in maternal aggressive behavior (number of bites directed at the intruder) after microinjection of the agonist at 0.2 and 1.0 æg/0.2 æl (1.6 ± 0.7 and 0.9 ± 0.3) into the DPAG compared to the saline group (5.5 ± 1.1). There was no dose-response relationship with the agonist. The present findings suggest that the 5-HT2A/2C receptor agonist has an inhibitory effect on maternal aggressive behavior when microinjected into the DPAG and no effect when microinjected into the MS. Ketanserin (1.0 æg/0.2 æl) decreased locomotion when microinjected into the DPAG and MS, but did not affect aggressive behavior. We interpret these findings as evidence for a specific role of 5-HT2A/2C receptors in the DPAG in the inhibition of female aggressive behavior, dissociated from those on motor activity.

Effects of exposure to a pyrethroid insecticide during lactation on the behavior of infant and adult rats

Cyhalothrin, a pyrethroid insecticide, was administered to female Wistar rats as a 0.02% solution plus 0.04% sucrose (w/v) in drinking water from whelping to pup weaning after 21 days of lactation. The pesticide did not change the maternal behavior of the dams as measured by the scoring system of Sderstein and Eneroth. The body weight of pups exposed to the pesticide and at age 90 days was not different from that of controls, and the motor activity of the pups measured in a simple photocell activity cage was not affected by pesticide treatment. Furthermore, no overt sings of neural toxicity were observed in the offspring. However, the treatment disrupted rat behavior in adulthood when assessed by using an inhibitory avoidance learning task. Thus, inhibitory avoidance tests carried out on rats at 90 days of age were capable of demonstrating neural toxicity of Cyhalothrin (0.02%) present only in the drinking water of dams during 21 days of lactation