Eventos adversos em uma unidade de internação psiquiátrica / Eventos adversos en una unidad de hospitalización psiquiátrica / Adverse events in a psychiatric hospitalization unit

RESUMO Objetivo descrever os eventos adversos presentes na internação psiquiátrica, analisando-os à luz da teoria do erro humano. Método pesquisa qualitativa, realizada em 2018 em um hospital psiquiátrico. Os dados foram coletados por entrevistas semiestruturadas com 15 profissionais de saúde da equipe multidisciplinar. A análise foi lexical por meio do software Alceste. Resultados evidenciaram-se eventos adversos medicamentosos por erros de administração ou por reações adversas a medicamentos, que produzem danos como impregnação, reações extrapiramidais associadas aos riscos de queda e broncoaspiração pela sonolência e/ou sedação. Outros danos relacionam-se à agressividade do paciente, que produz lesões corporais a si ou a outro, como durante uma tentativa de suicídio ou uso de violência como comportamento de fuga ou defesa. Considerações finais e implicações para a prática existem eventos adversos mais comuns nos ambientes de internação psiquiátrica que precisam ser de conhecimento da equipe de saúde mental porque demandam ações de mitigação por meio do fortalecimento dos sistemas de segurança do paciente. Os dados subsidiam ações para o fortalecimento dos sistemas de segurança nos ambientes de internação psiquiátrica e contribuem à reflexão do conceito de segurança do paciente na psiquiatria.

RESUMEN Objetivo describir los eventos adversos presentes en la hospitalización psiquiátrica, analizándolos a la luz de la teoría del error humano. Método investigación cualitativa, realizada en 2018 en un hospital psiquiátrico. Los datos se recolectaron a través de entrevistas semiestructuradas con 15 profesionales de la salud del equipo multidisciplinario. Se llevó a cabo el análisis léxico por medio del software Alceste. Resultados se evidenciaron eventos adversos por errores de administración o reacciones adversas al fármaco, que producen daños como impregnación y reacciones extrapiramidales asociadas al riesgo de caídas y broncoaspiración por somnolencia y / o sedación. Otros daños se relacionan con agresividad por parte del paciente, que produce daño corporal a sí mismo o a otro, como durante un intento de suicidio o uso de violencia como conducta de fuga o defensa. Conclusión e implicaciones para la práctica hay eventos adversos más comunes en entornos de hospitalización psiquiátrica que deben ser conocidos por el equipo de salud mental porque exigen acciones de mitigación a través del fortalecimiento de los sistemas de seguridad del paciente. Los datos reflejan la necesidad de implementar acciones para fortalecer los sistemas de seguridad en entornos de hospitalización psiquiátrica y contribuyen a la reflexión del concepto de seguridad del paciente en psiquiatría.

ABSTRACT Objective to describe the adverse events found in psychiatric hospitalization, analyzing them in the light of the human error theory. Method a qualitative research study, carried out in 2018 in a psychiatric hospital. The data were collected through semi-structured interviews with 15 health professionals from the multidisciplinary team. Analysis was of the lexical type using the Alceste software. Results adverse drug events were evidenced due to administration errors or adverse drug reactions, which produce harms such as impregnation and extrapyramidal reactions associated with the risks for falls and bronchoaspiration due to drowsiness and/or sedation. Other harms are related to the patient's aggressiveness, which produce bodily self-harm or harms to another person, such as during a suicide attempt or use of violence as an escape or defense behavior. Conclusion and implications for the practice some adverse events are more frequent in psychiatric hospitalization settings; such events need to be known by the mental health team, as they require mitigation actions through the strengthening of patient safety systems. The data subsidize actions for strengthening safety systems in psychiatric hospitalization settings and contribute to reflecting on the concept of patient safety in Psychiatry.

Investigação da presença e da influência do Epstein-Barr vírus na severidade da papilomatose laríngea / Investigation of the presence and influence of Epstein-Barr virus on the severity of laryngeal papilomatosis

A papilomatose laríngea é uma neoplasia benigna causada pelo papilomavírus humano (HPV), sendo os tipos 6 e 11 os mais comuns, e que ocorre em dois grupos etários, juvenil e adulto. A possível coinfecção viral tem sido sugerida em lesões de cabeça e pescoço; nesse sentido, o Epstein Barr vírus (EBV), que também apresenta tropismo por células epiteliais vem sendo estudado neste grupo de lesões. Os objetivos deste estudo foram genotipar os HPVs, investigar a presença de EBV-DNA por PCR e EBV-RNA por hibridização in situ. Além disso, associar a presença de EBV com a imunoexpressão de CD21, os resultados obtidos com a escala laringoscópica de Derkay et al. (1998) e com os dados clinicopatológicos. Oitenta casos de papilomatose laríngea, juvenil (n=36) e adulta (n=44), foram retrospectivamente analisados e subdivididos em grupos de menor e maior severidade, baseando-se na escala de Derkay. Todas as amostras foram HPV posivitas, com 49 casos HPV 6, 26 casos HPV 11, 4 casos HPV 6 e 11, e 1 caso HPV 16. A presença de EBV-DNA foi detectada em 9 amostras, entretanto EBV-RNA não foi não foi identificado em nenhuma amostra. Assim como a presença do EBV-DNA, a imunoexpressão de CD21 não se associou estatisticamente com quaisquer variáveis. A presença de HPV 6 foi mais comum em PLA e, o HPV 11 foi mais comum (p=0,02) e maior em casos de maior severidade (p=0,04), no grupo juvenil. A presença do EBV provavelmente não desempenha papel importante na progressão/severidade desta patologia(AU)

Laryngeal papillomatosis is a benign neoplasm caused by the human papillomavirus (HPV), been types 6 and 11 the most commonly related, and is divided into two groups: juvenile and adult. Viral coinfection has been suggested in head and neck lesions; in this sense, Epstein Barr virus (EBV), which also presents tropism for epithelial cells, has been studied in this group of lesions. The aims of this study are to perform HPV genotyping, investigate EBVDNA presence by PCR and EBV-RNA by in situ hybridization; and associate EBV presence with CD21 immunoexpression. Finally, the results were associated with Derkay laryngoscopic score. Eighty cases of laryngeal papillomatosis, juvenile (n = 36) and adult (n = 44) were retrospectively subdivided into low-risk and high-risk of severity based on the Derkay index. All samples were HPV-positive, with 49 cases of HPV 6, 26 cases of HPV 11, 4 cases of HPV 6 and 11, and 1 case of HPV 16. The presence of EBV-DNA was detected in 9 samples, however EBV-RNA was not identified in any sample. As the presence of EBV-DNA, the CD21 immunoexpression was not statistically associated with any variables. The presence of HPV 6 was more common in ALP, HPV 11 was more common (p = 0.02) and higher in cases of higher severity (p = 0.04) in juvenile group. The presence of EBV probably does not play an important role in the progression/severity of this pathology(AU)

Correlation between Expression of Peripheral IL-17 Protein and Aggression of Bipolar Mania / 法医学杂志

OBJECTIVE@#To explore the correlation between the interleukin-17 (IL-17) level of peripheral blood and aggression of bipolar mania.@*METHODS@#Thirty-six patients of bipolar mania were selected as experimental group by DSM-IV-TR and received treatment with quetiapine and lithium. Thirty-six healthy volunteers with similar age and gender were selected as control group. The level of IL-17 at baseline in each group and the level of IL-17 in the experimental group after treatment for 2, 4 and 8 weeks were detected by ELISA.@*RESULTS@#The level of IL-17 in experimental group at baseline, after treatment for 2 and 4 weeks were all significantly higher than that in control group. After 8 weeks treatment, there was no significant difference between the two groups (P > 0.05). After 2, 4 and 8 weeks treatment, the total score and aggression score of Young Mania Rating Score (YMRS) were significantly lower than the baseline level (P < 0.05). In experimental group, the level of IL-17 was positively correlated with the two scores of YMRS at baseline (P < 0.05).@*CONCLUSION@#Bipolar mania may be related to the up-regulation of IL-17. The level of IL-17 is related to the severity of manic symptoms at baseline, especially aggression symptom.

Utilidad farmacoclínica de los antidepresivos ISRS en la impulsividad y la agresividad / Utility of SSRI antidepressants in the treatment of impulsivity and aggression

Introducción: Estudios preliminares sobre neurobiología de la agresividad impulsiva destacaron el papel de la serotonina para inhibir la conducta violenta que se relacionaría con la impulsividad, pero no con la agresividad. En el ámbito carcelario las conductas agresivas e impulsivas presentan una alta prevalencia y requieren su abordaje por el equipo interdisciplinario de Salud Mental. Objetivos: Determinar la utilidad farmacoclínica de antidepresivos ISRS en el tratamiento de la impulsividad y la agresividad, y sus especificidades clínicas y poblacionales. Material y Método: Estudio observacional y transversal mediante evaluación de historias clínicas de 104 masculinos con pena privativa de la libertad. Se evaluaron psicopatológicamente y se valoraron los resultados obtenidos en 4 escalas de seguimiento clínico para impulsividad y agresividad. Al subgrupo con resultado positivo en al menos 2 escalas y en la evaluación clínica (n=30) se les indicó un ISRS (paroxetina o sertralina) a su plan farmacológico y se los reevaluaron en 2 tiempos posteriores. Se aplicaron parámetros estadísticos y se cumplimentó con requisitos ético-legales. Resultados: Al analizar las subescalas de la ABS hallamos que el parámetro de agresividad y el de desinhibición fueron los que más respondieron de forma significativa (25.96%, 21.43%; p<0.01). El análisis de la escala IRS arrojó que las subescalas de tiempo para toma de decisiones y de capacidad para diferir disminuyeron significativamente (p<0.01), mientras que la de agresividad y de paciencia/impaciencia tuvieron menor significación estadística (p<0.05). Conclusiones: Los inhibidores selectivos de recaptación de serotonina tienen eficacia y utilidad clínica en el tratamiento de pacientes con comportamientos impulsivo-agresivos con particularidades asociadas a otros fármacos, diagnóstico psicopatológico y tipo de agresividad.

Introduction: Preliminary Studies on neurobiology of impulsive aggression highlighted the role of serotonin to inhibit violent behavior that would be related to impulsivity, but not aggressive. In prisons, aggressive and impulsive behaviors have a high prevalence and require interdisciplinary team approach for Mental Health. Objectives: To determine the utility of SSRI antidepressants in the treatment of impulsivity and aggression, and its clinical and population specific. Material and method: Observational and transversal study through evaluation of medical records of 104 men in prision. Psychiatrically evaluated and the results obtained in four scales for clinical follow-up were evaluated impulsivity and aggressiveness. The subgroup with a positive result in at least 2 scales and clinical evaluation (n = 30) were prescribed an SSRI (paroxetine or ser traline) to your drug plan and the re-evaluated in two later times. Statistical parameters were applied and complied with ethical and legal requirements. Results: to analyze ABS ́s subscales we found that aggressiveness and disinhibition settings were the ones that responded significantly (25.96%, 21.43%; p<0.01). The analysis of the IRS scale showed that time for decision making scale and ability to differ subscales decreased significantly (p<0.01), while aggressiveness and patience/impatience ones had less statistical significance. Conclusions: Selective serotonin reuptake inhibitors have clinical utility and effectiveness in the treatment of patients with impulsive-aggressive behavior associated with drugs other particularities, psychopathological diagnosis and aggressive type

Ethanol during adolescence decreased the BDNF levels in the hippocampus in adult male Wistar rats, but did not alter aggressive and anxiety-like behaviors / O etanol durante a adolescência reduziu os níveis de BDNF no hipocampo de ratos Wistar machos adultos, mas não alterou os comportamentos agressivos e a ansiedade

Objective:To investigate the effects of ethanol exposure in adolescent rats during adulthood by assesssing aggression and anxiety-like behaviors and measuring the levels of inflammatory markers.Methods:Groups of male Wistar rats (mean weight 81.4 g, n = 36) were housed in groups of four until postnatal day (PND) 60. From PNDs 30 to 46, rats received one of three treatments: 3 g/kg of ethanol (15% w/v, orally, n = 16), 1.5 g/kg of ethanol (12.5% w/v, PO, n = 12), or water (n = 12) every 48 hours. Animals were assessed for aggressive behavior (resident x intruder test) and anxiety-like behaviors (elevated plus maze) during adulthood.Results:Animals that received low doses of alcohol showed reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus as compared to the control group. No significant difference was found in prefrontal cortex.Conclusions:Intermittent exposure to alcohol during adolescence is associated with lower levels of BDNF in the hippocampus, probably due the episodic administration of alcohol, but alcohol use did not alter the level agression toward a male intruder or anxiety-like behaviors during the adult phase.

Objetivo: Investigar os efeitos da exposição ao etanol em ratos adolescentes durante a idade adulta sobre os comportamentos agressivos e semelhantes à ansiedade, bem como sobre as medidas de níveis de marcadores inflamatórios.Métodos:Os grupos de ratos Wistar machos (peso médio de 81,4 g; n = 36) foram alojados em grupos de quatro até o dia pós-natal (DPN) 60. Entre os DPNs 30 e 46, os ratos receberam um dos três tratamentos: 3 g/kg de etanol (15% w/v, oralmente, n = 16), 1.5 g/kg de etanol (12,5% w/v, oralmente, n = 12), ou água (n = 12) a cada 48 horas. Os comportamentos agressivos (teste residente-intruso) e semelhantes à ansiedade (labirinto em cruz elevado) foram avaliados durante a idade adulta dos animais.Resultados:Os animais que receberam doses menores de álcool mostraram níveis reduzidos de fator neurotrófico derivado do cérebro (BDNF) no hipocampo quando comparados ao grupo controle. Nenhuma diferença significativa foi verificada no córtex pré-frontal.Conclusões:A exposição intermitente ao álcool durante a adolescência é associada com menores níveis de BDNF no hipocampo, provavelmente divido a administração episódica de álcool, mas o uso não alterou o nível de agressão contra o macho intruso ou os comportamentos semelhantes à ansiedade durante a fase adulta.

Tratamento farmacológico da impulsividade e do comportamento agressivo / Pharmacological treatment of impulsivity and aggressive behavior

A impulsividade aumentada e o comportamento agressivo ocorrem frequentemente em uma série de transtornos psiquiátricos e de doenças neurológicas. Duas abordagens de tratamento podem ser empregadas: o tratamento do transtorno ou da doença em que esses sintomas ocorrem ou o tratamento da impulsividade e do comportamento agressivo. Este segundo enfoque considera que há similaridades neurobiológicas subjacentes independentemente dos diagnósticos "primários" a que elas estejam associadas. O desequilíbrio entre os impulsos límbicos ascendentes, exercidos por estruturas como a amígdala, e os mecanismos de controle pré-frontais descendentes poderiam ser a razão última de um comportamento agressivo-impulsivo. Os papéis da serotonina, da noradrenalina e da dopamina foram amplamente investigados com relação ao comportamento impulsivo e agressivo e esses dados neuroquímicos foram ainda integrados ao modelo neuroanatômico, fornecendo as bases para a intervenção farmacológica sobre esses comportamentos.

Impulsivity and aggressive behavior occur frequently in a variety of psychiatric disorders and neurological diseases. Two lines of treatment could be employed, the treatment of the disorder or disease in which these symptoms occur or the treatment of the impulsivity and aggressive behavior itself. This second approach considers that there are neurobiological similarities underlying these behaviors regardless of the "primary" diagnoses with which they are associated. Imbalance between limbic bottom-up drives, exerted by structures like the amygdala, and prefrontal top-down control mechanisms could be the ultimate reason for an aggressive-impulsive behavior. The role of serotonin, noradrenalin and dopamine were comprehensively investigated with regards to impulsive and aggressive behavior and these neurochemical data were further integrated with the neuroanatomical model, providing the bases to the rational pharmacological approach of these behaviors.

Neurotoxicity and aggressiveness triggered by low-level lead in children: a review / Neurotoxicidad y agresividad desencadenadas por bajos niveles de plomo en niños: una revisión

Lead-induced neurotoxicity acquired by low-level long-term exposure has special relevance for children. A plethora of recent reports has demonstrated a direct link between low-level lead exposure and deficits in the neurobehavioral-cognitive performance manifested from childhood through adolescence. In many studies, aggressiveness and delinquency have also been suggested as symptoms of lead poisoning. Several environmental, occupational and domestic sources of contaminant lead and consequent health risks are largely identified and understood, but the occurrences of lead poisoning remain numerous. There is an urgent need for public health policies to prevent lead poisoning so as to reduce individual and societal damages and losses. In this paper we describe unsuspected sources of contaminant lead, discuss the economic losses and urban violence possibly associated with lead contamination and review the molecular basis of lead-induced neurotoxicity, emphasizing its effects on the social behavior, delinquency and IQ of children and adolescents.

La neurotoxicidad adquirida inducida por la exposición prolongada a bajos niveles de plomo tiene una importancia especial en los niños. Una plétora de publicaciones recientes ha demostrado el vínculo directo existente entre la exposición a bajos niveles de plomo y el déficit en el desempeño neuroconductual-cognitivo manifestado desde la infancia hasta el final de la adolescencia. En numerosos estudios, la agresividad y la delincuencia juvenil también se han considerado síntomas de la intoxicación por plomo. Se han identificado y explicado ampliamente varias fuentes ambientales, laborales y domésticas de contaminación por plomo y los riesgos resultantes para la salud, pero aún son numerosos los casos de intoxicación por plomo. Se necesitan urgentes políticas de salud pública para prevenir la intoxicación por plomo de manera de reducir los daños y las pérdidas, tanto individuales como para la sociedad. En este artículo se describen algunas fuentes no sospechadas de contaminación por plomo y se discuten las pérdidas económicas y la violencia urbana posiblemente asociada con este tipo de contaminación. Además, se hace una revisión de las bases moleculares de la neurotoxicidad inducida por plomo, con énfasis en sus efectos sobre el comportamiento social, la delincuencia juvenil y el coeficiente intelectual de los niños y los adolescentes.

Control of psychomotor agitation and aggressive behavior in patients with autistic disorder: a retrospective chart review / Controle da agitação psicomotora e agressividade em pacientes com autismo: estudo retrospectivo de revisão de prontuário

OBJECTIVE: To evaluate the efficacy of pharmacotherapy on the symptoms of psychomotor agitation and aggressive behavior in a sample of patients with autistic spectrum disorder. METHOD: The charts of all patients with a diagnosis of autistic spectrum disorder, receiving care for psychomotor agitation and/or aggressive behavior in two psychiatric outpatient departments between 2001 and 2006, were reviewed. The Clinical Global Impression-Severity and -Improvement scales (CGI-S and CGI-I) were applied to the data retrieved from the charts. RESULTS: The majority of the 26 patients included were treated with second-generation antipsychotics. A positive, statistically significant correlation was found between the implementation of pharmacotherapy and a reduction in CGI-S scores (p<0.05). Treatment response in patients with no mental retardation was better than in those mentally retarded (p<0.05). The majority of patients in whom clinical improvement was found following implementation of treatment had participated in at least one form of intervention therapy in addition to the principal treatment (p<0.05). CONCLUSION: Second-generation antipsychotics seem to reduce psychomotor agitation and aggressive behavior in patients with autistic spectrum disorder; however, further studies are required to evaluate the side effects of these drugs in relation to their beneficial effects.

OBJETIVO: Avaliar a eficácia do tratamento farmacológico dos sintomas de agitação psicomotora e agressividade em amostra de pacientes com transtorno do espectro autista. MÉTODO: Foram revisados os prontuários de pacientes com diagnóstico de transtorno do espectro autista que procuraram atendimento por apresentarem agitação psicomotora e/ou heteroagressividade, atendidos entre 2001 e 2006, em dois ambulatórios de psiquiatria. Para avaliação da evolução dos pacientes aplicou-se às informações do prontuário a escala de Impressão Clínica Global Sintomas (ICG-S) e a Impressão Clínica Global Melhora (ICG-M). RESULTADOS: A maioria dos 26 pacientes estava em tratamento com antipsicóticos de segunda geração. Houve correlação positiva e estatisticamente significativa entre a introdução do tratamento farmacológico e a redução nos escores da ICG-S (p<0,05). A evolução do tratamento farmacológico foi melhor para os pacientes sem retardo mental do que para aqueles com retardo mental (p<0,05). A maioria dos pacientes que obteve melhora clínica com o tratamento participava de ao menos uma intervenção auxiliar ao tratamento principal (p<0,05). CONCLUSÃO: Os antipsicóticos de segunda geração parecem reduzir a agitação psicomotora e agressividade em pacientes com transtorno do espectro autista no Brasil. É necessário que se avaliem os efeitos colaterais em relação aos efeitos benéficos dessas drogas.

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.

Effects of sodium valproate and carbamazepine on food competition aggression in pigeons

Valproate and carbamazepine (CAR) have been proposed as adjunct alternatives for the control of aggression in psychiatric patients, although no definite conclusions have been reached. We examined the effects of these drugs on food competition offensive aggression and other behaviors in high- and low-aggression food-restricted pigeons. These were divided into pairs containing previously ranked high-aggression (N = 10 pairs) and low-aggression females (N = 10 pairs). In Experiment 1, a pigeon in each pair of high- and low-aggression subjects was treated daily with an oral dose of sodium valproate (50 mg kg-1 mL saline-1) for 15 days. The other animal received the vehicle. On days 1, 7, and 15, food competition trials (10 min) were performed 60 min after treatment. In Experiment 2, one pigeon in each pair was treated daily with an oral dose of CAR (20 mg kg-1 mL saline-1) for 15 days. Each pair was submitted to a food competition trial on days 1, 7, and 15 of treatment. Valproate (15 days of treatment) selectively decreased the time spent in offensive aggression (control: 102.7 ± 9.3 vs valproate: 32.7 ± 9.2 s; P < 0.001, ANOVA-2-TAU) of high-aggression pigeons. This was also the case for 7 and 15 days of CAR treatment (control: 131.5 ± 8.9 vs CAR: 60.4 ± 5.3, P < 0.01, and control: 122.7 ± 7.1 vs CAR: 39.1 ± 5.2; P < 0.001, ANOVA-2-TAU, respectively). Thus, the two anticonvulsive drugs have a similar effect on food competition aggression in pigeons.

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.

Pharmacological evaluation of Pachyrrhizus erosus (L) seeds for central nervous system depressant activity.

The research work deals with the screening of ethanol and chloroform extracts of Pachyrrhizus erosus seeds for central nervous system (CNS) depressant activity. The Pachyrrhizus erosus seed is known to contain rotinoids, flavonoids and phenylfuranocoumarin derivatives as chemical components and is reported to have antifungal, antisecretory, insecticides, antibacterial and spasmolytic activity. Since seeds of Pachyrrhizus erosus is used as folk medicine in treatment of insomnia, we made an attempt to study its CNS depressant effect. The different activities studied were potentiation of pentobarbitone-induced sleep, test for locomotor activity, effect on muscle co-ordination, antiaggressive and antianxiety activities. The result of the study reflected that ethanol extract of the seeds (150 mg/kg, p.o) decreased locomotor activity, produced muscle relaxation and showed antianxiety and antiaggressive activity.

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.

Enkephalinergic involvement in substantia nigra in the modulation of hypothalamically-induced predatory attack behavior.

The present study was carried out in five cats which did not attack the rats spontaneously. Predatory attack on an anaesthetized rat was elicited by electrical stimulation of lateral hypothalamus at a mean current strength of 650 microA. The attack was accompanied by minimal affective display and culminated in neck biting. Microinfusions of DAME (delta-alanine methionine enkephaline) in 500 ng dose in substantia nigra facilitated the predatory attack and there was a significant reduction in the threshold current strength for affective display as well as somatomotor components. Microinfusions of naloxone, an opioid antagonist in 1.0 microg dose when DAME effect was at its peak reversed the facilitatory effects and the threshold returned to the control levels within 10 minutes of naloxone infusion at the same locus. Microinfusions of naloxone alone in similar dosage completely blocked the predatory attack response as indicated by an increase in the threshold current strength for somatomotor as well as affective display components. The somatomotor were completely inhibited and could not be elicited even when the current strength was increased to 1000 microA. Control injections of saline in similar volumes (0.5 microl) failed to produce any response Microinfusions of naloxone in lower dose (250 ng) failed to produce any blocking effect. These findings indicate that hypothalamically elicited predatory attack is facilitated by enkephalinergic mechanisms operating at the midbrain level.

Action of selective serotonin reuptake inhibitor on aggressive behavior in adult rat submitted to the neonatal malnutrition

The effect of the malnutrition during suckling on the aggressiveness was investigated in adult rats treated or not with citalopram, a selective serotonin reuptake inhibitor (SSRI). The animals were divided into two groups according to the diet used: nourished groupó the rats received the control diet with 23 per cent protein during the life; and malnourished groupó the rats had its mothers submitted to diet with 7.8 per cent protein during suckling. At 120 days of age, each group was sub-divided according to the treatment: acute ó consisting a single i.p. injection of saline solution or 20-mg/Kg citalopram; chronic ó consisting the single injections (1 per day during 14 days) of saline or 20 mg/Kg citalopram. The acute or chronic treatment with SSRI reduces aggressive response in nourished rats, but not in malnourished ones. Thus, the malnutrition during the critical period of brain development seems to induce durable alterations in the function of the serotoninergic neurotransmission

Risperidone for controlling aggressive behavior in a mentally retarded child: a case report.

Risperidone is an atypical antipsychotic agent with dopamine and serotonin antagonistic effects. It is an effective treatment for reducing aggressive behavior in adults with mental retardation. The use of risperidone in a severely mental retarded child with aggression is described. Risperidone was able to reduce the aggressive behavior in this patient. No serious side effect was found. This case illustrated that risperidone is effective and well tolerated in treating aggressive behavior in children with severe mental retardation. However, the anti-aggressive effect of risperidone in mentally retarded children remains to be seen in a larger sample-size study.

Reduction of intraspecific aggression in adult rats by neonatal treatment with a selective serotonin reuptake inhibitor

Most studies suggest that serotonin exerts an inhibitory control on the aggression process. According to experimental evidence, this amine also influences growth and development of the nervous tissue including serotoninergic neurons. Thus, the possibility exists that increased serotonin availability in young animals facilitates a long-lasting effect on aggressive responses. The present study aimed to investigate the aggressive behavior of adult rats (90-120 days) treated from the 1st to the 19th postnatal day with citalopram (CIT), a selective serotonin reuptake inhibitor (20 mg/kg, sc, every 3 days). Aggressive behavior was induced by placing a pair of rats (matched by weight) in a box (20 x 20 x 20 cm), and submitting them to a 20-min session of electric footshocks (five 1.6-mA - 2-s current pulses, separated by a 4-min intershock interval). When compared to the control group (rats treated for the same period with equivalent volumes of saline solution), the CIT group presented a 41.4 percent reduction in the duration of aggressive response. The results indicate that the repeated administration of CIT early in life reduces the aggressive behavior in adulthood and suggest that the increased brain serotoninergic activity could play a role in this effect

Quantification of behaviour in social colonies of rhesus monkey.

It is necessary to use experimental animals with behavioural, physiological and disease susceptibility pattern similar to man so that the results have a clinical predictive value. For such studies the non-human primate is the animal of choice. Rhesus monkey is a good choice for this purpose but information about its behaviour is fragmentary. In order to obtain a quantitative baseline data for psychopharmacological studies, a protocol has been developed to score various social and solitary behaviours in adult male and female rhesus monkeys. The study was conducted on rhesus monkeys in a social colony of one male and seven female living in a semi-restricted environment. The behavioural patterns were quantitated so as to compare effect on various components of behaviour. Aggressiveness and vigilance were prominent in the male while social affiliative behaviour was dominant in the female. Other behavioural responses were of similar magnitude in both sexes. It is however necessary to have data with some standard CNS active agents on these behavioural protocol. Therefore, initially the behavioural effects of amphetamine and haloperidol were studied. Significant effects observed following d-amphetamine (1-4 mg/kg, im); it induced dose dependent suppression of social behaviour (approach, contact, grooming), feeding, hypervigilance, stereotypy and oral hyperkinesia. On the other hand haloperidol (0.01-0.04 mg/kg, im) produced decrease in social and solitary behaviour and marked cataleptic posture. It is possible to quantitate drug effects on various aspects of behaviour of the rhesus monkey and to develop neuropsychitric models with the help of this protocol for use in study of drug effects on behaviour.

Evaluation of inhibitory effect of diphenhydramine on benzodiazepine dependence in rats.

Effect of diphenhydramine was investigated on withdrawal signs in lorazepam dependent rats. Physical dependence was produced by giving lorazepam admixed with the food in the following dose schedule: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 (mg/kg, daily x days). The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), body temperature, reaction time to pain, foot shock aggression (FSA) and audiogenic seizures. Diphenhydramine was administered orally in the dose schedules of once daily (10, 20 and 40 mg/kg) and twice daily (5, 10 and 20 mg/kg) in separate groups during the withdrawal period. The withdrawal signs observed in control group (without diphenhydramine) were hyperkinesia, hyperthermia, hyperaggression and audiogenic seizures. Hyperkinesia and hyperthermia were blocked in all the groups of diphenhydramine-treated rats. FSA was inhibited only by diphenhydramine (10 and 20 mg/kg) given twice daily. Audiogenic seizures were completely blocked by once daily (20 and 40 mg/kg) as well as twice daily (20 mg/kg) doses of diphenhydramine. It may be concluded that diphenhydramine exerts a protective effects on benzodiazepine withdrawal syndrome.

Effect of calcium channel blockers on withdrawal syndrome of lorazepam in rats.

Effects of calcium channel blockers were investigated on withdrawal signs in lorazepam dependent rats. Physical dependence was produced by giving lorazepam admixed with the food in the following dose schedule: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 (mg/kg daily x days). Parameters such as body weight, food intake, spontaneous locomotor activity (SLA), body temperature, reaction time to pain, foot shock-aggression (FSA) and audiogenic seizures were observed during the period of administration of lorazepam and after its withdrawal. Calcium channel blockers viz. verapamil, nifedipine and nimodipine in different doses were administered orally twice daily in separate groups during the withdrawal period. The withdrawal signs observed in control group (without calcium channel blockers) were hyperkinesia, hyperthermia, hyper-aggression and audiogenic seizures. The administration of verapamil (5-20 mg/kg), nifedipine (1.75-7 mg/kg) and nimodipine (5-20 mg/kg) during the withdrawal period of lorazepam showed dose dependent significant blockade of all the withdrawal signs. Audiogenic seizures were completely blocked by 20 mg/kg dose of verapamil and nimodipine while nifedipine was partially effective. It may be concluded that calcium channel blockers exert protective effects on benzodiazepine withdrawal syndrome.