Representações sociais de pessoas com câncer em cuidados paliativos sobre a morfina / Social representations of people with cancer in palliative care on morphine

INTRODUÇÃO: A dor se apresenta como sintoma frequente nas pessoas com câncer, e os opioides são os fármacos de escolha para o seu alívio. Dentre eles tem-se a morfina, que é um dos mais utilizados. OBJETIVOS: Descrever as representações sociais de pessoas com câncer em cuidados paliativos sobre a morfina; Analisar tais representações e suas implicações para a adesão ou não a esse opioide no tratamento/alívio da dor do câncer; Propor estratégias de cuidados afinadas às representações das pessoas com câncer que requerem o uso de morfina. MÉTODO: Pesquisa com abordagem qualitativa, do tipo descritiva e exploratória, realizada em uma instituição pública hospitalar. Os participantes foram pessoas com câncer atendidas no Ambulatório. Critérios de inclusão: maiores de 18 anos, com índice ≥ 50% na Escala de Karnofsky (KPS) e prescrição analgésica de morfina. Critérios de exclusão: presença de dor de moderada a intensa no momento da coleta de dados; e aqueles com comprometimento verbal, cognitivo e/ou psiquiátrico. Os dados foram coletados por questionário e entrevista semiestruturada. Os dados do questionário foram analisados por estatística descritiva simples e percentual, e aos conteúdos verbais aplicou-se a análise de conteúdo do tipo lexical, com o uso do software Alceste. Projeto aprovado pelos Comitês de Ética em Pesquisa da instituição proponente e cooperante, com pareceres no 3.296.128 e no 3.453.968, respectivamente. Todos os participantes assinaram o Termo de Consentimento Livre e Esclarecido. RESULTADOS: A média de idade foi de 54,7 anos; sexo feminino (69,7%); predomínio da religião evangélica (60,6%); 81,8% afirmaram seguir corretamente a prescrição da morfina; na Escala de Karnofsky, 45,5% apresentaram índice de 60%, evidenciando a necessidade de assistência ocasional, mas com capacidade de trabalhar; a intensidade da dor pela escala visual analógica variou entre leve (grau 1) e moderada (grau 4), ambas com 21,2% de respostas. O processamento dos dados no Alceste gerou dois blocos, o primeiro com a Classe 1, que expressa a representação medicamentosa do tratamento com a morfina e os fatores associados a esse tratamento; o segundo foi composto pelas Classes 2 e 3 e expressam as relações sociais envolvidas no contexto do tratamento, o vínculo da pessoa que usa morfina com o mundo que a cerca, bem como a relação estabelecida com esse medicamento, o conhecimento sobre a morfina e as atitudes adotadas diante desse uso. Houve ambiguidade nas representações da morfina, colocando-a entre a dor e o temor, pois a indicam como um importante recurso para alívio/tratamento da dor do câncer, mas sinalizam que também pode trazer repercussões negativas associadas aos seus efeitos. CONSIDERAÇÕES FINAIS: Apesar de haver aderência dos pacientes à morfina, a opiofobia ainda precisa ser combatida por meio de estratégias que façam circular informações que possam reconstruir representações sobre a morfina e seu uso terapêutico. A educação terapêutica por meio da atuação de equipe multidisciplinar se destaca como uma boa estratégia de difusão de informações seguras sobre o uso de opioides.

INTRODUCTION: Pain is a frequent symptom in people with cancer, and opioids are the drug of choice for its relief, including morphine, which is one of the most used. OBJECTIVES: To describe the social representations of people with cancer in palliative care about morphine; To analyze such representations and their implications for adherence or not to this opioid in the cancer pain treatment/relief; To propose care strategies related to the representations of people with cancer that require the use of morphine. METHOD: Descriptive and exploratory research with a qualitative approach, carried out in a public hospital. The participants were people with cancer treated at the clinic. Inclusion criteria: over 18 years old, with an index ≥ 50% on the Karnofsky Scale (KPS) and morphine as an analgesic medication prescribed. Exclusion criteria: presence of moderate to severe pain at the time of data collection; and those with verbal, cognitive and/or psychiatric impairment. Data was collected by questionnaire and semi-structured interview. The questionnaire data were analyzed using simple and percentage descriptive statistics, and the verbal content was analyzed using lexical content with the Alceste software. Project approved by the Research Ethics Committees of the proposing and cooperating institution, with opinions No. 3,296,128 and 3,453,968, respectively. All participants signed the Free and Informed Consent Form. RESULTS: The average age was 54.7 years; female gender (69.7%); prevalence of the evangelical religion (60.6%); 81.8% said they correctly followed the prescription of morphine; on the Karnofsky Scale, 45.5% had an index of 60% showing the need for occasional assistance, but with the ability to work; pain intensity by visual analog scale ranged from mild (grade 1) to moderate (grade 4), both with 21.2% responses. The data processing at Alceste generated two blocks, the first with class 1, which expresses the drug representation of the treatment with morphine and the factors associated with that treatment; the second was composed of Classes 2 and 3 and expresses the social relationships involved in the context of the treatment, the bond of the person who uses morphine with the world around her, as well as the relationship established with this medicine, the knowledge about the morphine and the attitudes towards the use of the medicine. There was ambiguity in the representations of morphine, placing it between pain and fear, as they indicate it as an important resource to relieve/treat cancer pain, but it can also bring negative repercussions associated with its effects. FINAL CONSIDERATIONS: Despite patient adherence to morphine, opiophobia still needs to be fought through strategies that spread information that can reconstruct representations about morphine and its therapeutic use. Therapeutic education through the work of a multidisciplinary team stands out as a good strategy to disseminate safe information about the use of opioids.

INTRODUCCIÓN: El dolor es un síntoma frecuente en las personas con cáncer y los opioides son los fármacos de elección para su alivio; entre ellos está la morfina, que es uno de los más utilizados. OBJETIVOS: Describir las representaciones sociales de las personas con cáncer en cuidados paliativos sobre la morfina; analizar tales representaciones y sus implicaciones para la adherencia o no a este opioide en el tratamiento / alivio del dolor producido por el cáncer; Proponer estrategias de cuidados en sintonía con las representaciones de las personas con cáncer que requieren el uso de morfina. MÉTODO: Investigación con enfoque cualitativo, descriptivo y exploratorio, realizada en un hospital público. Los participantes fueron personas con cáncer tratadas en modalidad ambulatorial. Criterios de inclusión: mayores de 18 años, con índice ≥ 50% en la Escala de Karnofsky (KPS) y prescripción analgésica de morfina. Criterios de exclusión: presencia de dolor de moderado a intenso en el momento de la recogida de datos; y aquellos con comprometimiento verbal, cognitivo y/o psiquiátrico. Datos recogidos mediante cuestionario y entrevista semiestructurada. Los datos del cuestionario se analizaron mediante estadística descriptiva simple y porcentual y el contenido verbal fue sometido a análisis de contenido de tipo lexical, utilizándose el software Alceste. Proyecto aprobado por los Comités de Ética en Investigación de la institución proponente y cooperante, con dictámenes núm. 3.296.128 y 3.453.968, respectivamente. Todos los participantes firmaron una declaración de Consentimiento Libre e Informado. RESULTADOS: La edad promedio fue de 54,7 años; sexo femenino (69,7%); predominio de la religión evangélica (60,6%). El 81,8% afirmó que seguía correctamente la prescripción de morfina. En la Escala de Karnofsky, el 45,5% presentó un índice del 60%, lo que indica la necesidad de asistencia ocasional, pero con capacidad para trabajar. La intensidad del dolor, según la escala visual analógica (EVA), varió de leve (grado 1) a moderado (grado 4), ambos con 21,2% de respuestas. El procesamiento de datos en el software Alceste generó dos bloques: el primero con la Clase 1, que expresa la representación farmacológica del tratamiento con morfina y los factores asociados a ese tratamiento; el segundo estaba compuesto por las Clases 2 y 3 y expresa las relaciones sociales involucradas en el contexto del tratamiento, el vínculo de la persona que usa morfina con el mundo que la rodea, así como la relación que establece con ese medicamento, el conocimiento sobre la morfina y las actitudes adoptadas con respecto a su uso. Hubo ambigüedad en las representaciones de la morfina, pues se la situó entre el dolor y el miedo: los participantes la señalaron como un recurso importante para el alivio/tratamiento del dolor oncológico, pero también mencionaron la posibilidad de repercusiones negativas asociadas a sus efectos. CONSIDERACIONES FINALES: A pesar de la adherencia de los pacientes a la morfina, la opiofobia aún debe combatirse mediante estrategias que hagan circular información que permita la reconstrucción de las representaciones sobre la morfina y su uso terapéutico. La educación terapéutica mediante la actuación de un equipo multidisciplinario descolla como una buena estrategia para difundir información segura sobre el uso de opioides.

Mujeres argentinas y usos de drogas: análisis sociohistórico del uso femenino de sustancias psicoactivas en Argentina (1860-1930) / Argentinian women and the uses of drugs: A sociohistorical analysis of female drug use in Argentina (1860-1930)

RESUMEN Este trabajo describe casos expuestos por expertos de los ámbitos legislativo y médico-legal periodístico, en los que se reporta el consumo de sustancias psicoactivas por parte de mujeres de Argentina, entre 1878 y 1930. Se presentan antecedentes sobre mujeres y usos de distintos fármacos, se analizan las intervenciones médicas que utilizan sustancias psicoactivas sobre el cuerpo femenino, y se detallan los casos de mujeres consumidoras desde las miradas expertas. En este periodo, los discursos expertos no buscaron comprender la especificidad femenina del consumo, sino promover el tema drogas como un problema. Esto se produce utilizando tres prototipos: la víctima de un marido enfermo, la prostituta que envicia a los débiles de espíritu (criminal nata), y la joven virtuosa que contraviene la ley del padre y sucumbe en la toxicomanía. Cada figura refuerza la necesidad de intervención estatal y control social.

ABSTRACT This article describes cases presented by experts from the legislative and medical-legal fields regarding the use of psychoactive substances among Argentinian women from 1878 to 1930. Background information is presented regarding the relationship between women and the use of different drugs, medical interventions on the female body where psychoactive substances were used are analyzed, and experts' descriptions of cases of female drug users are detailed. Experts' discourses during this period did not attempt to comprehend the specificities of female consumption but were rather used to position the issue of drug use as a social problem. This was done using three prototypes: the victim of a sick husband; the prostitute who encourages drug use among the weak in spirit (natural-born criminals); and the virtuous young woman who succumbs to drug addiction in spite of her father's rule. Each figure reinforces the need for state intervention and increased social control.

[Synchronic effect of curcumin and swimming training on depression level in morphine dependent male mice]

Background: There is need to more research because of extent drug trade in country and diversity of proposal cures such as non pharmacological ways including exercise and herbal supplements medicine

Objective: The aim of this study was investigation of synchronic effect of Curcumin and swim training on depression in morphine dependent male mice

Methods: In an experimental research, 40 Albino NMRI male mice with 19- 21 gr were selected as subjects and they were divide randomly to care groups of control, morphine, swim training, Curcumin, Swim training+ Curcumin. Subjects swam 60 min/day, 5 days/week for 1 week with receiving Curcumin. Then, they were taken morphine [2.5 mg/ml/kg] for 5 days with swim training. Therefore FST was done and after 10 days this test was taken again

Results: Training increased swimming activity time, but it had no significant effect on immobility and climbing activities. At this period, Curcumin supplement caused increasing the time of climbing activities and no alteration in immobility and swimming times. Curcumin supplement with swim training caused increasing immobility time and decreasing swimming time, but it had no significant effect on climbing activities time

Conclusion: The results of this research showed that morphine consumption didn't cause depression. Also, combination of Curcumin supplement and swim training didn't cause depression decreasing in morphine consumption term

EEG characteristics of medial prefrontal cortex in rats with morphine dependent place preference under shuttling condition / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the correlation between EEG characteristics of medial prefrontal cortex (mPFC) and drug-seeking behavior of rats with morphine dependent place preference under shuttling condition.</p><p><b>METHODS</b>Forty rats were randomly divided into four groups (n = 10): morphine PL group, NS PL group, morphine IL group and NS IL group. After embeding the electrode in prelimbic (PL) or infralimbic (IL) cortex of each group by brain stereotaxic operation, the model of morphine dependent conditioned place preference (CPP) in rats was established. The differences of EEG wave percentage in mPFC were telemetered and analyzed when rats shuttled before and after the model.</p><p><b>RESULTS</b>After the model, the withdrawal symptoms were evident in morphine PL and IL group, and the activity time and distance in white box were increased obviously. Compared with control group, after the model, the EEG in morphine PL group showed that: when the rats shuttled to white box, 8 wave decreased obviously, P wave increased obviously. When the rats shuttled to black box, brain waves showed opposite changes. The EEG in morphine IL group showed that: when the rats shuttled to white box, a wave increased obviously, P and a wave decreased obviously. When the rats shuttled to black box, the brain wave had no significant differences compared with control group.</p><p><b>CONCLUSION</b>The EEG changes are different in PL and IL cortex of morphine CPP rats under shuttling condition, and the EEG changes are also different when rats shuttling to white or black box. There is possibly different mechanism, when different drug-seeking environmental cues caused EEG changes in different regions of mPFC.</p>

Changes of telemetry electrical activity in the infralimbic cortex of morphine-dependent rats with extinguished drug-seeking behavior / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes of telemetry electrical activity in the infralimbic cortex (IL) of morphine-dependent rats with extinguished drug-seeking behavior.</p><p><b>METHODS</b>SD rats were randomly divided into model group and control group and received operations of brain stereotaxic electrode embedding in the IL. The rats in the model group were induced to acquire morphine dependence and then received subsequent extinction training, and the changes of electrical activity in the IL were recorded with a physical wireless telemetry system.</p><p><b>RESULTS</b>In rats with morphine dependence, the time staying in the white box was significantly longer on days 1 and 2 after withdrawal than that before morphine injection and that of the control rats, but was obviously reduced on days 1 and 2 after extinction training to the control level. Compared with the control group, the morphine-dependent rats on day 2 following withdrawal showed significantly increased β wave and decreased δ wave when they stayed in the white box but significantly increased δ wave and decreased α wave and β wave when they shuttled from the black to the white box. On day 2 of extinction, the model rats, when staying in the white box, showed significantly decreased θ wave compared with that of the control rats group but decreased β wave and θ wave and increased δ wave compared with those in the withdrawal period. When they shuttled from black to white box, the model rats showed decreased δ wave and increased α wave and β wave compared with those in the withdrawal period.</p><p><b>CONCLUSION</b>Morphine-dependent rats have abnormal changes of electrical activity in the IL in drug-seeking extinction to affect their drug-seeking motive and inhibit the expression and maintenance of drug-seeking behaviors.</p>

Research by Psychiatrists of Chosun Chongdokbu Hospital and Keijo Imperial University in Korea during Japanese Colonial Rule / 신경정신의학

Eighty-three of 114 original articles and abstracts of research published by neuropsychiatrists of Chosun Chongdokbu Hospital (the Japanese colonial government hospital in Korea) and Keijo (Seoul) Imperial University Hospital during the Japanese colonial period (1910-1945) in journals including Shinkeigaku-zassi (Neurologia), Seishin-shinkei-gaku zassi (Psychiatria Et Neurologia Japonica), and The Journal of Chosun (Korea) Medical Association were reviewed. Most articles were on clinical research based on descriptive and biological psychiatry while only 4 articles were on dynamic psychiatry, probably because Japanese pioneers in psychiatry had introduced German psychiatry into Japan during the 1880s. The first paper was written by Dr. Shim Ho-sub. Professor Kubo of Keijo (Seoul) Imperial University published most articles, followed by Dr. Hikari, Dr. Hattori, and Dr. Sugihara. There were more articles on symptomatic psychosis and morphine addiction, followed by general paralysis, schizophrenia, neurological diseases, narcolepsy, epilepsy, and neurasthenia. The meaningful articles even for today were comparative studies between Japanese and Koreans and articles on opioid use disorder in Korea. Authors reported a markedly lower rate of psychotic inpatients in the population of Koreans compared with Japanese. Japanese researchers argued that, because of simpleness in social life in Korea and less violence or excitement in symptoms, Korean mental patients could be cared for by family or members of the community, or be treated by shamanism rather than bringing them to a public mental hospital, and poverty also prohibited hospital care. Finding of higher ratio of schizophrenia to manic-depressive psychosis among Koreans than Japanese was discussed in relation to delayed cultural development of Korea compared to Japan. In addition, traditional customs prohibiting marriage between relatives in Korea was related to low prevalence of manic-depressive psychosis, local endemic malaria was related to low prevalence of general paresis, and poor general hygiene was related to high prevalence of epilepsy. Unclear (undifferentiated) form of psychotic symptoms including hallucination and delusion was reported in more Koreans than Japanese. Also Korean patients showed a more atypical form in diagnosis. Authors added that they had found no culture-specific mental illness in Korea. However, no Korean psychiatrists were included as author in such comparative studies. Comparative studies on constitution between Koreans and Japanese mental patients and prisoners were also unique. However, no Korean psychiatrists participated in such comparative studies. In studies on morphine addiction in Koreans, Japanese researchers argued that such studies were necessary to prevent introduction of morphine-related criminal phenomena to Japan. Meanwhile, Dr. Kubo had left a notion on adaptation problems of Japanese living in the foreign country, Korea. Nevertheless he reported nothing about psychosocial aspects of mental illness in relation to political, cultural, and economic difficulties Koreans were experiencing under the colonial rule of Japan. These general trends of studies based on German biological and descriptive psychiatry and policies of colonial government to isolate "dangerous" mental patients in hospital appeared to reflect colonial or ethnopsychiatry of those days. These policy and research trends seem to have worsened stigma attached to mental disorders. Japanese tradition of psychiatric research was discontinued by return home of Japanese scholars with the end of WWII and colonial rule.

Comparative proteomic analysis of the nucleus accumbens during extinction and reinstatement of morphine dependence / Análisis proteómico comparativo del núcleo accumbens durante laextinción y recaída de la dependencia a la morfina

BACKGROUND: The aim of this study was to detect differentially expressed proteins in the nucleus accumbens between the states of extinction and reinstatement of morphine addiction. Numerous studies on the neurobiological mechanisms concerning drug craving and relapse have been reported to date, but data on their relationship with the underlying key molecular mechanisms involved remain limited. METHODS: In this study, 40 male SpragueDawley rats were equally randomized into a saline group and a morphine group. Both groups received drug selfadministration training, after which extinction models were established naturally. The groups were further divided into two subgroups for extinction and reinstatement tests. Cerebral nucleus accumbens masses were measured for total protein extraction. Twodimensional electrophoresis was performed to determine differential protein spots. These differential proteins were then enzymolysed and identified using mass spectrography. RESULTS: The proteins were classified as fatty acidbinding protein, serine/threonine protein phosphatase 2A catalytic subunit beta isoform, serine/threonine protein phosphatase 2A catalytic subunit alpha isoform, serine/threonine protein phosphatase 2A regulatory subunit B² subunit gamma or heat shock protein 90 cochaperone CDC37. CONCLUSION: Significant changes in five proteins were detected between extinction and reinstatement. These proteins are correlated with phosphorylation and the tricarboxylic acid cycle.

ANTECEDENTES: El objetivo de este estudio fue detectar las proteínas diferencialmente expresadas en el núcleo accumbens entre los estados de extinción y recaída de la adicción a la morfina. Hasta la fecha se han reportado numerosos estudios en relación con los mecanismos neurobiológicos del deseo incontenible y recaída en el consumo de drogas, pero los datos sobre su relación con los mecanismos moleculares fundamentales subyacentes implicados, siguen siendo limitados. MÉTODO: En este estudio, 40 ratas machos SpragueDawley fueron por igual asignadas de manera aleatoria a un grupo salino y un grupo de morfina. Ambos grupos recibieron entrenamiento de autoadministración de drogas, después de lo cual se establecieron modelos de extinción de manera natural. A su vez, los grupos fueron luego subdivididos en dos subgrupos para realizar pruebas de extinción y recaída. Se procedió a medir las masas cerebrales del núcleo accumbens para la extracción total de proteína. Se realizó una electroforesis bidimensional para determinar manchas proteicas diferenciales. Estas proteínas diferenciales fueron entonces sometidas a enzimólisis e identificadas mediante espectrografía de masa. RESULTADOS: Las proteínas fueron clasificadas como proteína de unión a ácidos grasos, isoforma beta de la subunidad catalítica serinatreonina proteína fosfatasa 2A, isoforma alfa de la subunidad catalítica serinatreonina proteína fosfatasa 2A, subunidad gamma subunidad B" de la serinatreonina proteína fosfatasa 2A, o la proteína CDC37 cochaperona 90 de choque térmico. CONCLUSIÓN: Se detectaron cambios significativos en cinco proteínas entre la extinción y la recaída. Estas proteínas están correlacionadas con la fosforilación y el ciclo del ácido tricarboxílico.

Inhibition of the reinstatement of morphine-induced place preference in rats by high-frequency stimulation of the bilateral nucleus accumbens / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery. Many studies have identified a central role of the nucleus accumbens (NAc) in addiction. Deep brain stimulation (DBS) has the advantages of being reversible, adjustable, and minimally invasive, and it has become a potential neurobiological intervention for addiction. The purpose of our study was to investigate whether high-frequency DBS in the NAc effectively attenuates the reinstatement of morphine seeking in morphine-primed rats.</p><p><b>METHODS</b>A morphine-dependent group of rats was given increasing doses of morphine during conditioned place preference training. A control group of rats was given equal volumes of saline. After the establishment of this model, withdrawal syndromes were precipitated in these two groups by administering naloxone, and the differences in withdrawal symptoms between the groups were analyzed. Electrodes for DBS were implanted in the bilateral shell of the NAc in the experimental group. The rats were stimulated daily in the NAc for 5 hours per day over 30 days. Changes in the conditioned place preference test and withdrawal symptoms in the rats were investigated and place navigation studies were performed using the Morris water maze. The data were assessed statistically with one-way analysis of variance (ANOVA) followed by Tukey's tests for multiple post hoc comparisons.</p><p><b>RESULTS</b>High-frequency stimulation of the bilateral NAc prevented the morphine-induced reinstatement of morphine seeking in the conditioned place preference test. The time spent in the white compartment by rats following 30 days of DBS ((268.25 ± 25.07) seconds) was not significantly different compared with the time spent in the white compartment after relapse was induced by morphine administration ((303.29 ± 34.22) seconds). High-frequency stimulation of the bilateral NAc accelerated the innate decay of drug craving in morphine-dependent rats without significantly influencing learning and memory.</p><p><b>CONCLUSION</b>Bilateral high-frequency stimulation of the shell of the NAc may be useful as a novel therapeutic modality for the treatment of severe morphine addiction.</p>

Expression of GAP-43 in midbrain ventral tegmental area of morphine withdrawal rats / 法医学杂志

OBJECTIVE@#To observe the protein expression of growth associated protein-43 (GAP-43) in midbrain ventral tegmental area in morphine withdrawal rats at different time, and to evaluate the effect of GAP-43 on morphine withdrawal memory.@*METHODS@#Rat models of morphine dependent 1 week, 2 weeks and 4 weeks were established by morphine hydrochloride intraperitoneal injection with increasing doses to establish natural withdrawal. The protein expression of GAP-43 in midbrain ventral tegmental area was observed by immunohistochemical staining and the results were analyzed by Image-Pro Plus 5.1 image analysis system.@*RESULTS@#With prolongation of dependent time, the expression of GAP-43 was decreased then increased in midbrain ventral tegmental area.@*CONCLUSION@#GAP-43 could play a role in morphine withdrawal memory in midbrain ventral tegmental area.

Suppressive effects of Rosa damascena essential oil on naloxone-precipitated morphine withdrawal signs in male mice

This research was done to test the effect of Rosa damascena essential oil on withdrawal signs of naloxone-precipitated morphine in male mice. Morphine dependence was induced by injection [IP] three times daily at doses of 50, 50 and 75 mg/kg, respectively, for 3 days. On day 4, after the last administration of morphine, Rosa damascena essential oil was administered at different concentrations [5, 2 and 40%, IP] 30 min before administration of naloxone [5 mg/kg, IP]. The following actions were taken as signs of withdrawal and records taken for jumping as a number and scores of 0 to 3 were given for incidences of grooming, teeth chattering, rearing, writing, diarrhea, wet dog shakes and climbing during a 30 min period. Results showed that different concentrations of Rosa damascena essential oil significantly reduced signs of morphine withdrawal compared to the control group in terms of number of jumps [p < 0.05 and p < 0.01], grooming, teeth chattering, rearing, climbing, wet dog shakes and writhing, but not for diarrhea [p < 0.05]. In conclusion it seems that GABAergic activity induced by flavonoids from Rosa damascena essential oil can alleviate signs of morphine withdrawal, but further studies need to be done to better understand this mechanism

effect of oral feeding of Tribulus terrestris L. on sex hormone and gonadotropin levels in addicted male rats

Opioids can exert adverse effects on the body. Morphine, an opioid drug, reduces hormone levels and fertility, and causes sexual activity disorders. Tribulus terrestris [TT] is a traditional herbal medicine used to enhance sexual activities. This study investigates the possible role of TT on sex hormones and gonadotropins with the intent to show its usefulness in treating fertility disorders in opioid users. In this experimental study, we randomly divided 48 rats into four groups: i. control, ii. TT-treated, iii. addicted and iv. TT-treated addicted. Watersoluble morphine was administrated orally for 21 days to induce addiction, after which the treated groups 2 and 4 received plant-mixed pelleted food [6.25%] orally for four weeks. At the end of the treatment period, the sex hormone and gonadotropin levels of all rats' sera were determined by radioimmunoassay and Elisa kits. The data obtained were statistically analyzed using the one-way analysis of variance, followed by post-hoc Tukey test. P<0.05 was considered significant. The addicted group had a significantly lower luteinizing hormone [LH] level than the control group [p<0.027]. LH levels increased significantly in the TT-treated addicted group [p<0.031]. The testosterone level in the treated addicted group was lower than the treated control group. The addicted group had a significantly low testosterone level [p<0.001]. The estrogen level was significantly [p<0.002] lower in the addicted group than in the control group. In addition, there was a significant difference between the treated addicted group and the treated control group [p<0.048]. The treated control group had a significant increase in its progesterone level [p<0.002]. Overall, except for follicle-stimulating hormone [FSH], morphine reduced most of the gonadotropins and sexual hormones. Whereas TT caused a considerable increase [p<0.05] in the hormones in the treated addicted group, there was only a slight increase in the treated control group. Oral consumption of TT could markedly antagonize the reduction of sex hormones and gonadotropins [except for FSH] due to morphine addiction

role of GABAB receptors in morphine self-administration

There is only little information about the effects of GABA receptors agonist and antagonist on morphine self-administration. Present study was designed to assess role of GABAB receptors in the regulation of morphine-reinforced self-administration. This study was performed in four groups of rats: [1] Saline group, which received saline in the self-administration session. [2] Morphine group, which received morphine in saline solution in the self-administration session. [3] Baclofen + Morphine group, which received both baclofen 20 min before self- administration test and morphine in the self-administration session. [4] Phaclofen + Morphine group, which received both phaclofen 20 min before self- administration test and morphine in the self-administration session. The number of lever pressing and self-infusion were recorded. Morphine significantly increased the number of active lever pressing dose dependently in self-administration session in comparative with saline group. Administration of baclofen, 20 min before morphine self-administration produced significant decrease in the initiation of morphine self-administration during all session. Conversely, pre-treatment of phaclofen increased the number of active lever pressing and self-infusion in this test. Our results indicated a short-term treatment by baclofen, reduced morphine-maintenance response in a dose-dependent manner, suggesting that GABAB receptor agonists could be useful for reversing the neuroadaptations related to opiates

[ effect of carbenoxolone on morphine-induced withdrawal symptoms in rats]

The exact mechanisms of morphine dependence and withdrawal syndrome remain unclear. Many studies have been performed to find a drug for prevention of withdrawal syndrome. The aim of this study was to evaluate the effect of carbenoxolone [a gap junction inhibitor] on morphine withdrawal syndrome in male rats. In this experimental study, adult male Sprague Dawley rats with weights between 225 and 275 g were selected randomly and divided into 8 groups. Each group consisted of 8 rats. In order to induce dependency, morphine was injected subcutaneously for nine days [1[st] day: 5mg/kg, 2[nd] and 3[rd] days: 10 mg/kg, 4[th] and 5[th] days: 15 mg/kg, 6[th] and 7[th] days: 20 mg/kg, 8[th] and 9[th] days: 25 mg/kg]. On the ninth day only the morning dose of morphine was injected, then control group and treatment groups received IP injection of saline [1 ml/kg] and IP injection of carbenoxolone [5, 25, 50, 100 mg/kg] respectively. After 30 min all groups received IP injection of naloxone [4 mg/kg] and the withdrawal signs including: jumping, rearing, genital grooming, abdominal writhing, body grooming and wet dog shake, were recorded for 60 minutes. Our results showed that carbenoxolone not only decreased all withdrawal signs, but also reduced the total withdrawal scores, significantly. In conclusion we found that carbenoxolone as a gap junction inhibitor was effective in decreasing the symptoms of morphine withdrawal syndrome.

Study on acting mechanism of anti-morphine conditioned place preference between aqueous extract of Corydalis yanhusuo and L-THP and comparison of their effects / 中国中药杂志

<p><b>OBJECTIVE</b>To study the acting mechanism of anti-morphine conditioned place preference (CPP) between aqueous extract of Corydalis yanhusuo and L-THP and compare their effects.</p><p><b>METHOD</b>The CPP model was established by injecting morphine in rats with a increasing dose for 10 days, with the initial dose of 10 g x kg(-1) and the final dose of 100 g x kg(-1), 10 mg x kg(-1) was increased each day, thus 100 mg x kg(-1) was injected by d 10. Having been treated with differential doses (2, 1 and 0.5 g x kg(-1)) of C. yanhusuo (containing L-THP: 0.153, 0.077 and 0.038 mg x kg(-1) respectively) and L-THP (3.76, 1.88 and 0.94 mg x kg(-1)) for six days, the CPP effect in rats was detected. Both colorimetry and immunohistochemistry methods were adopted to detect the content of glutamate neurotransmitter in each brain region and the expression of NR2B in VTA-NAc-PFC neuroanatomical circuit.</p><p><b>RESULT</b>Compared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76 and 1.88 mg x kg(-1)) groups showed a notably shorter retention period of rats in white boxes (morphine-accompanied boxes) (P < 0.05 or P < 0.01) and remarkably lower glutamic acid content in VTA, NAc and PFC and NR2B expression.</p><p><b>CONCLUSION</b>Both C. yanhusuo and L-THP can substantially inhibit the effect of morphine CPP, reduce the increasing glutamic acid content in VTA-NAc-PFC neuroanatomical circuit and down-regulated NR2B expression, which may be one of mechanisms on reducing the effect of morphine CPP. C. yanhusuo preparations containing L-THP (1 x ) showed 24-fold effect of L-THP monomer of single application in terms of the behaviouristics of inhibitory effect on CPP as well as the similarity in terms of transmitter glutamic acid of in VTA-NAc-PFC neuroanatomical circuit and pharmacological mechanism of NR2B.</p>

Repeated morphine pretreatment reduces glutamatergic synaptic potentiation in the nucleus accumbens induced by acute morphine exposure / 生理学报

Repeated exposure to morphine leads to the addiction, which influences its clinical application seriously. The glutamatergic projection from prefrontal cortex (PFC) to the nucleus accumbens (NAc) plays an important role in rewarding effects. It is still unknown whether morphine exposure changes PFC-NAc synaptic transmission. To address this question, in vivo field excitatory postsynaptic potentials (fEPSPs) induced by electric stimulating PFC-NAc projection fibers were recorded to evaluate the effect of acute morphine exposure (10 mg/kg, s.c.) on glutamatergic synaptic transmission in NAc shell of repeated saline/morphine pretreated rats. It was showed that acute morphine exposure enhanced fEPSP amplitude and reduced paired-pulse ratio (PPR) in saline pretreated rats, which could be reversed by following naloxone injection (1 mg/kg, i.p.), an opiate receptor antagonist. However, repeated morphine pretreatment significantly inhibited both the enhancement of fEPSP amplitude and reduction of PPR induced by acute morphine exposure. Those results indicate that the initial morphine exposure enhances PFC-NAc synaptic transmission by pre-synaptic mechanisms, whereas morphine pretreatment occludes this effect.

The role of the spinal cord inducible nitric oxide synthase in morphine dependence and naloxone-precipitated withdrawal rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore if induced nitric oxide in the spinal cord mediates withdrawal syndrome in morphine-dependent rats.</p><p><b>METHODS</b>Male SD rats weighing 200-250 g were employed in the present study. To set up morphine dependence model, rats were subcutaneously injected with morphine (twice a day, for 5 d). The dose of morphine was 10 mg/kg in the first day and was increased by 10 mg/kg each day. On day 6, 4 h after the injection of morphine (50 mg/kg), morphine withdrawal syndrome was precipitated by an injection of naloxone (4 mg/kg, ip). Inducible nitric oxide synthase (iNOS) inhibitors aminoguanidine (AG) was intrathecally injected 30 min before the administration of naloxone. All the rats were divided into four groups: control group, dependence group, withdrawal group, AG group. Morphine withdrawal score, touch evoked agitation scores (TEA scores), immunohistochemical and Western blot technique were used to evaluate morphine withdrawal response and the expression of iNOS in the spinal cord.</p><p><b>RESULTS</b>Intrathecal injection of iNOS inhibitors AG could alleviate morphine withdrawal symptoms. Morphine withdrawal scores and touch evoked agitation scores in AG group were significantly lower than that of withdrawal group (P < 0.05). iNOS positive neurons in dorsal horn of AG group were significantly lower than that of withdrawal group (P < 0.05). Level of iNOS protein in spinal cord of AG group was significantly lower than that of withdrawal group (P < 0.05).</p><p><b>CONCLUSION</b>Induced nitric oxide in the spinal cord may mediate withdrawal syndrome in morphine-dependent rats.</p>

The different roles of the spinal protein nNOS and iNOS in morphine naloxone-precipitated withdrawal response / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of intrathecal injection of neuronal nitric oxide synthase (nNOS) inhibitors 7-Nitroindazole (7-Ni) and inducible nitric oxide synthase(iNOS) inhibitors aminoguanidine (AG) on the behavioral changes of morphine-induced dependent and withdrawal rats; the expression of Fos, nNOS and iNOS in spinal cord.</p><p><b>METHODS</b>To set up morphine dependence model, rats were subcutaneously injected with morphine (twice a day, for 5 d). The dose of morphine was 10 mg/kg in the first day and was increased by 10 mg/ kg every day. On day 6, 4 h after the injection of morphine (50 mg/kg), morphine withdrawal syndrome was precipitated by an injection of naloxone (4 mg/kg ip). 7-Ni, an nNOS inhibitor or iNOS inhibitors AG were intrathecally injected 30 min before the administration of naloxone respectively. The scores of morphine withdrawal symptom and morphine withdrawal-induced allodynia were observed. One hour after naloxone-precipitated withdrawal, Fos protein expression was assessed by immunohistochemical analysis and Western blot was used to detect the expression of nNOS and iNOS in the rat spinal cord.</p><p><b>RESULTS</b>Intrathecal administration of nNOS inhibitor 7-Ni and iNOS inhibitors AG decreased the scores of morphine withdrawal, attenuated morphine withdrawal-induced allodynia and also inhibited the increase of Fos protein expression in the spinal cord of morphine withdrawal rats. nNOS and iNOS positive neurons in dorsal horn in nNOS group and iNOS group were significantly lower than that in withdrawal group. Compared with withdrawal group, level of nNOS and iNOS protein in spinal cord in nNOS group and iNOS group were significantly lower.</p><p><b>CONCLUSION</b>It is suggested that nNOS and iNOS in the spinal cord may contribute to naloxone-precipitated withdrawal in rats and may play different roles in the above-mentioned effect.</p>

Changes of protein kinase A expressions in central amygdaloid nuclei during the process of chronic morphine-induced conditioned place aversion in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore neurobiological mechanisms of the withdrawal-induced aversion. The changes of protein kinase A were measured in central amygdaloid nucleic (CeA) of conditioned place aversion (CPA) model rats.</p><p><b>METHODS</b>(1) All 72 male SD rats were divided into three groups, model group (MN group), and control group (MS group and SN group). MN group was injected with morphine,6.5 days, 10 mg/kg, intraperitoneally (ip), twice per day, naloxone injection, 0.3 mg/kg, ip, along with conditioned place aversion training, to develop the CPA model. The MS group was administrated equivalent volume of morphine and saline. Also the SN group was injected with equivalent volume of saline and naloxone. (2) During the process of morphine-induced CPA, the expression of protein kinase A was assayed with immunohistochemistry in the CeA.</p><p><b>RESULTS</b>In the MN group, protein kinase A expressions in the CeA occurred adaptive changes at different points of CPA (P < 0.05). Protein kinase A expressions after establishment(Day7,134.43 +/- 4.481, P < 0.05), and after extinction (Day 13, 141.01 +/- 3.360, P < 0.01), and after reinstatement (Day 14,137.18 +/- 40.330, P < 0.05) were also lower than those before the establishment of the CPA (Day 5, 124.48 +/- 6.722). However, PKA expressions were not significantly different both in MS group (P > 0.05)and SN group (P > 0.05).</p><p><b>CONCLUSION</b>(1) Protein kinase A expression, in turn regulating the aversion expression, in the CeA probably is a key pathway contributing to the development of CPA. (2) The neuroadaptation mediated by protein kinase A may be one of the important molecular underpinnings of CPA.</p>

Effect of Berberine on Depression- and Anxiety-Like Behaviors and Activation of the Noradrenergic System Induced by Development of Morphine Dependence in Rats

The purpose of this study was to evaluate whether berberine (BER) administration could attenuate depression- and anxiety-like behaviors and increase corticotrophin-releasing factor (CRF) and tyrosine hydroxylase (TH) expression following chronic morphine withdrawal in rats. Male rats were exposed to chronic, intermittent, escalating morphine (10~50 mg/kg) for 10 days. After the last morphine injection, depression- and anxiety-like beahvior associated with morphine discontinuation persisted for at least three days during withdrawal without any change in ambulatory activity. Daily BER administration significantly decreased immobility in the forced swimming test and increased open-arm exploration in the elevated plus maze test. BER administration also significantly blocked the increase in hypothalamic CRF expression and TH expression in the locus coeruleus (LC) and the decrease in hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression. Taken together, these findings demonstrated that BER administration significantly reduced morphine withdrawal-associated behaviors following discontinuation of repeated morphine administration in rats, possibly through modulation of hypothalamic CRF and the central noradrenergic system. BER may be a useful agent for treating or alleviating complex withdrawal symptoms and preventing morphine use relapses.

MEK inhibitors suppressed expression of NOS in spinal cord of morphine-induced dependent and withdrawal rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of intrathecal injection of mitogen-activated protein kinases inhibitors U0126 on the behavioral changes of morphine-induced dependent and withdrawal rats and the expression of nitric oxide synthase (NOS) in spinal cord.</p><p><b>METHODS</b>All the rats were divided into 4 groups: control group, dependent group, withdrawal group, U0126 group (5 microg). Global withdrawal score, Touch evoked agitation scores (TEA score), immunohistochemical and Western blot technique were undertaken to evaluate behavioral changes and expression of FOS, nNOS and iNOS in spinal cord respectively.</p><p><b>RESULTS</b>The results showed that intrathecal administration of U0126 significantly alleviated withdrawal symptom, withdrawal scores of U0126 group (22.5 +/- 4.09) were significantly lower than than those of withdrawal group (28.6 +/- 4.89) (P < 0.05). TEA scores of withdrawal group were 13.5 +/- 2.55, which were significantly higher than those of U0126 group (10.0 +/- 2.76, P < 0.05). Fos-like positive neurons in dorsal horn of withdrawal group were 380 +/- 71, which were higher than those of U0126 group(287 +/- 54, P < 0.05). Also nNOS and iNOS positive neurons in dorsal horn of U0126 group were 180 +/- 32, 10.8 +/- 2.8 respectively, which were significantly lower than that of withdrawal group (239 +/- 45, 16.8 +/- 5.1, P < 0.05). Compared with withdrawal group, levels of nNOS and iNOS protein in spinal cord of U0126 group were significantly lower.</p><p><b>CONCLUSION</b>MEK inhibitors could alleviate withdrawal symptom of morphine-induced dependent rats and could suppress expression of NOS in spinal cord, and extracellular signal-regulate kinase (ERK) might involve the expression of NOS in spinal cord.</p>