Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Perspectives on access to in vitro fertilization in Portugal / Perspectivas sobre o acesso aos tratamentos de fertilidade em Portugal / Visión de los utilizadores sobre el acceso a los tratamientos de fertilidad en Portugal

OBJECTIVE: To analyze users' reasons for choosing in vitro fertilization treatment in public or private services and to identify their suggestions for improving fertility treatment. METHODS: A qualitative study using an interpretative approach was conducted. Fifteen semi-structured interviews were conducted with patients undergoing in vitro fertilization treatment (nine women, one man and five couples) at home or at their workplace in the districts of Viana do Castelo, Braga, Porto and Lisbon, Portugal, between July 2005 and February 2006. RESULTS: Users evaluated access to in vitro fertilization treatment in public and private services based mainly on their individual experiences and called for more access to less costly, faster and friendlier care with suitable facilities, appropriate time management and caring medical providers. These perceptions were also associated with views on the need for fighting stigmatization of infertility, protecting children's rights and guaranteeing sustainability of health care system. Interviewees sought to balance reduced waiting time and more attentive care with costs involved. The choice of services depended on the users' purchase power and place of residence and availability of attentive care. CONCLUSIONS: Current national policies on in vitro fertilization treatment meet user's demands of promoting access to, and quality, availability and affordability of in vitro fertilization treatment. However, their focus on legal regulation and technical-scientific aspects contrasts with the users' emphasis on reimbursement, insurance coverage and focus on emotional aspects of the treatment. The study showed these policies should ensure insurance coverage, participation of user representatives in the National Council for Assisted Reproductive Technology, promotion of infertility research and certification of fertility laboratories.

OBJETIVO: Analisar as motivações para escolha de tratamentos de fertilização in vitro em serviços públicos e privados, bem como identificar propostas que melhorem a qualidade desses. MÉTODOS: Estudo qualitativo e interpretativo, baseado em 15 entrevistas semiestruturadas com pessoas que tentaram conceber por meio de técnicas de procriação medicamente assistida em Portugal (nove mulheres, um homem e cinco casais). As entrevistas foram realizadas entre julho de 2005 e fevereiro de 2006 nos distritos de Viana do Castelo, Braga, Porto e Lisboa, em casa ou no local de trabalho dos entrevistados. RESULTADOS: Os usuários avaliaram o acesso aos tratamentos de fertilidade no serviço público ou privado sobretudo com base nas suas experiências individuais, reclamando acesso mais barato, rápido e amigável, em espaços adequados, com gestão apropriada dos tempos de espera e serviços médicos atenciosos. Tais percepções foram associadas a visões sobre a necessidade de combater a estigmatização da infertilidade e defender os direitos da criança e a sustentabilidade do sistema de saúde. Os entrevistados procuraram equilibrar a redução do tempo de espera e cuidados mais atenciosos com os custos envolvidos. A escolha dos serviços dependeu da renda e do local de residência dos usuários, além da existência de cuidados atenciosos. CONCLUSÕES: As atuais políticas nacionais vão ao encontro das expetativas dos utilizadores ao promover o acesso aos tratamentos de fertilidade e a sua qualidade, mas distanciam-se delas ao enfatizarem a regulação jurídico-legal e a dimensão técnico-científica da qualidade na procriação medicamente assistida em detrimento do acionamento de seguros de saúde e da valorização de aspetos emocionais. As políticas a implementar passam pela cobertura obrigatória dos tratamentos pelos seguros de saúde, pela inclusão de um representante dos usuários no Conselho Nacional de Procriação Medicamente Assistida, pela promoção da investigação sobre infertilidade em Portugal e pela certificação dos laboratórios que realizam testes de fertilidade.

OBJETIVO: Analizar las motivaciones de usuarios para escogencia de tratamientos de fertilización in vitro en servicios públicos y privados e identificar propuestas que mejoren la calidad de los mismos. MÉTODOS: Estudio cualitativo con abordaje interpretativa, basado en 15 entrevistas semi-estructuradas con personas que intentaron concebir por medio de técnicas de procreación con asistencia médica en Portugal (nueve mujeres, un hombre y cinco matrimonios). Las entrevistas fueron realizadas entre julio de 2005 y febrero de 2006 en los distritos de Viana do Castelo, Braga, Porto y Lisboa, en casa o en el lugar de trabajo de los entrevistados. RESULTADOS: Los usuarios evaluaron el acceso a los tratamientos de fertilidad en el servicio público o privado principalmente con base en sus experiencias individuales, reclamando acceso más barato, rápido y amigable, en espacios adecuados, con gestión apropiada de los tiempos de espera y servicios médicos atentos. Tales percepciones fueron asociadas a visiones sobre la necesidad de combatir la estigmatización de infertilidad y defender los derechos del niño y la sustentabilidad del sistema de salud. Los entrevistados buscaron equilibrar la reducción del tiempo de espera y cuidados más atentos con los costos financieros involucrados. La escogencia de los servicios dependió del capital económico y del lugar de residencia de los utilizadores y de la existencia de cuidados atentos CONCLUSIONES: Las actuales políticas nacionales van en paralelo con las expectativas de los utilizadores al promover el acceso a los tratamientos de fertilidad y su calidad, pero se separan de ellas al enfatizar la regulación jurídico-legal y la dimensión técnico-científica de la calidad en la procreación con asistencia médica en detrimento de la activación de seguros de salud y de la valorización de aspectos emocionales. Las políticas a implementar pasan por la cobertura obligatoria de los tratamientos por los seguros de salud, la inclusión de un representante de los utilizadores en el Consejo Nacional de Procreación Con Asistencia Médica, la promoción de la investigación sobre infertilidad en Portugal y la certificación de los laboratorios que realizan pruebas de fertilidad.

Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine

Female rats are intensely affected by cocaine, with estrogen probably playing an important role in this effect. Progesterone modulates the GABA system and attenuates the effects of cocaine; however, there is no information about its relevance in changing GABA synthesis pathways after cocaine administration to female rats. Our objective was to investigate the influence of progesterone on the effects of repeated cocaine administration on the isoenzymes of glutamic acid decarboxylase (GAD65 and GAD67) mRNA in brain areas involved in the addiction circuitry. Ovariectomized, intact and progesterone replacement-treated female rats received saline or cocaine (30 mg/kg, ip) acutely or repeatedly. GAD isoenzyme mRNA levels were determined in the dorsolateral striatum (dSTR) and prefrontal cortex (PFC) by RT-PCR, showing that repeated, but not acute, cocaine decreased GADs/β-actin mRNA ratio in the dSTR irrespective of the hormonal condition (GAD65: P < 0.001; and GAD67: P = 0.004). In the PFC, repeated cocaine decreased GAD65 and increased GAD67 mRNA ratio (P < 0.05). Progesterone replacement decreased both GAD isoenzymes mRNA ratio after acute cocaine in the PFC (P < 0.001) and repeated cocaine treatment reversed this decrease (P < 0.001). These results suggest that cocaine does not immediately affect GAD mRNA expression, while repeated cocaine decreases both GAD65 and GAD67 mRNA in the dSTR of female rats, independently of their hormonal conditions. In the PFC, repeated cocaine increases the expression of GAD isoenzymes, which were decreased due to progesterone replacement.

Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin

The objective of the present study was to determine if the acute behavioral effects of cocaine acutely administered intraperitoneally (ip) at doses of 5, 10 and 20 mg/kg on white male CF1 mice, 90 days of age, would be influenced by leptin acutely administered ip (at doses of 5, 10 and 20 æg/kg) or by endogenous leptin production enhanced by a high-fat diet. The acute behavioral effects of cocaine were evaluated in open-field, elevated plus-maze and forced swimming tests. Results were compared between a group of 80 mice consuming a balanced diet and a high-fat diet, and a group of 80 mice fed a commercially available rodent chow formula (Ralston Purina) but receiving recombinant leptin (rLeptin) or saline ip. Both the high-fat-fed and rLeptin-treated mice showed decreased locomotion in the open-field test, spent more time in the open arms of the elevated plus-maze and showed less immobility time in the forced swimming test (F(1,68) = 7.834, P = 0.007). There was an interaction between diets and cocaine/saline treatments in locomotion (F(3,34) = 3.751, P = 0.020) and exploration (F(3,34) = 3.581, P = 0.024). These results suggest that anxiolytic effects and increased general activity were induced by leptin in cocaine-treated mice and that low leptin levels are associated with behavioral depression. Chronic changes in diet composition producing high leptin levels or rLeptin treatment may result in an altered response to cocaine in ethologic tests that measure degrees of anxiety and depression, which could be attributed to an antagonistic effect of leptin.

Effect of pilocarpine mouthwash on salivary flow

Pilocarpine is a cholinergic agonist that increases salivary flow and has been used to treat xerostomia. Oral intake is the most frequent route of administration. Adverse effects are dose-dependent and include sudoresis, facial blushing and increased urinary frequency. The objective of the present study was to evaluate the effects of topical pilocarpine solutions as mouthwashes on salivary flow and their adverse effects on healthy subjects. Forty volunteers received 10 ml 0.5, 1 and 2 percent pilocarpine solutions or 0.9 percent saline in a randomized, double-blind, placebo-controlled manner. Salivation was measured before and 45, 60 and 75 min after mouth rinsing for 1 min with 10 ml of saline or pilocarpine solutions. Vital signs were measured and ocular, gastrointestinal and cardiovascular symptoms, anxiety and flushing were estimated using visual analog scales. There was a dose-dependent increase in salivation. Salivation measured after 1 and 2 percent pilocarpine (1.4 +/- 0.36 and 2.22 +/- 0.42 g, respectively) was significantly (P<0.001) higher than before (0.70 +/- 0.15 and 0.64 +/- 0.1 g), with a plateau between 45 and 75 min. Cardiovascular, visual, gastrointestinal and behavioral symptoms and signs were not changed by topical pilocarpine. Mouth rinsing with pilocarpine solutions at concentrations of 1 to 2 percent induced a significant objective and subjective dose-dependent increase in salivary flow, similar to the results reported by others studying the effect of oral 5 mg pilocarpine. The present study revealed the efficacy of pilocarpine mouthwash solutions in increasing salivary flow in healthy volunteers, with no adverse effects. Additional studies on patients with xerostomia are needed

Plasma insulin levels are increased by sertraline in rats under oral glucose overload

Recognition and control of depression symptoms are important to increase patient compliance with treatment and to improve the quality of life of diabetic patients. Clinical studies indicate that selective serotonin reuptake inhibitors (SSRI) are better antidepressants for diabetic patients than other drugs. However, preclinical trials have demonstrated that not all SSRI reduce plasma glucose levels. In fact, fluoxetine increases and sertraline decreases glycemia in diabetic and non-diabetic rats. In the present study we evaluated plasma insulin levels during fasting and after glucose overload after treatment with sertraline. Adult male Wistar rats were fasted and treated with saline or 30 mg/kg sertraline and submitted or not to glucose overload (N = 10). Blood was collected and plasma insulin was measured. The mean insulin levels were: fasting group: 25.9 + or - 3.86, sertraline + fasting group: 31.10 + or - 2.48, overload group: 34.1 + or - 3.40, and overload + sertraline group: 43.73 + or - 5.14 æU/ml. Insulinemia was significantly increased in the overload + sertraline group. There were no differences between the other groups. No difference in glucose/insulin ratios could be detected between groups. The overload + sertraline group was the only one in which a significant number of individuals exceeded the upper confidence limit of insulin levels. This study demonstrates that sertraline increases glucose-stimulated insulin secretion without any change in peripheral insulin sensitivity

Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats

Diabetic patients have a 20 percent higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg), moclobemide (30 mg/kg), clonazepam (0.25 mg/kg), fluoxetine (20 mg/kg) sertraline (30 mg/kg) or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50 percent glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine and moclobemide increased blood glucose at different times after the glucose overload. Sertraline neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocin-induced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, sertraline neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether sertraline is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia

Pup age and aggressive behavior in lactating rats

High levels of aggressive behaviors against intruders in the nest area are displayed by female rats during the first 10 days after delivery, declining thereafter to very low levels, even though lactation continues. Cross-fostering experiments were undertaken to test the hypothesis that pup age may affect aggression in lactating rats. The behavior of females on the 8th day after delivery when raising fostered 8-day-old pups was compared to that of females on the 8th postpartum day raising older pups (18 days old) for the last 5 days, and females on the 18th day after delivery raising fostered 18-day-old pups were compared to females in the same postpartum period nursing younger pups (8 days of age at the time of the maternal aggression test) for 5 days. Pup retrieval activity and plasma prolactin level were also analyzed. Females on the 8th postpartum day nursing 18-day-old pups were less aggressive than females in the same postpartum period, but with 8-day-old pups. Likewise, females on the 18th postpartum day nursing younger pups were more aggressive and presented higher levels of prolactin than females nursing older pups. Thus, pup development can alter the natural decline of maternal aggressive behavior

Effect of estrogen and neuroleptics on prolactin secretion and immunoreactive prolactin cells

The use of estrogen and dopamine receptor antagonists is associated with elevated prolactin levels and, in rats, chronic estrogen treatment is also associated with lactotroph proliferation. In this study, haloperidol, fluphenazine, sulpiride and metoclopramide, alone or combined with estradiol, were administered to Wistar rats. Pituitary weight, serum prolactin levels and percent of immunoreactive prolactin cells in the anterior pituitary glands were determined at the end of 60 days of treatment. The pituitary weight of rats treated with estrogen alone or in combination with other drugs was significantly higher than the control group. The serum prolactin level was higher than the upper confidence limit in all but three of the 90 treated rats. While in the control group the percent of immunoreactive prolactin cells was 20 per cent, administration of the neuroleptic drugs and metoclopramide increased this percent to approximately 30 per cent, and estrogen alone or in combination with one of the neuroleptic drugs increased it to approximately 40 per cent. The results presented here demonstrate the elationship between prolactin secretion and prolactin cell number when different neuroleptics and related drugs are used.

Inhibition of enteropathogenic Escherichia coli adhesion to HeLa cells by serum of infants with diarrhea and by cord serum

We have studied the effect of serum from infants with diarrhea and of cord serum on the localized adherence of enteropathogenic Escherichia coli (EPEC) to HeLa cells. Serum samples from 16 infants with diarrhea due to EPEC of serotypes O55:H6, O111: H-, O111:H2, O119:H6 and O142:H6 were used. The adherence ability of EPEC strains belonging to serotypes identical to (homologous) or different from (heterologous) those isolated from the infants' feces was highly inhibited by samples of infant serum collected both during the acute phase of the illness and upon discharge from the hospital. These data confirm the development of antibodies against EPEC adhesins and the cross-reaction between different EPEC serotypes. Cord serum inhibited the localized adherence of EPEC strains at different levels according to the serotype of the strain studied. These results suggest that the placental transfer of adhesin-related antibodies does not protect the newborn against EPEC infections, since half of our patients were less than 30 days old

Serviço de informaçoes sobre substâncias psicoativas. Caraterísticas da informaçao sobre drogas / Psychoactive substances information service. Characteristics of the provision of drug information

Este trabalho apresenta a an lise das consultas realizadas a um serviço de informaçöes sobre substâncias psicoativas, em 42 meses de funcionamento. As 1.284 consultas foram feitas através de uma linha telef"nica, havendo contato direto com um plantonista, com manutençäo do anonimato, caso houvesse interesse do usu rio. Constatou-se que, apesar de ampla variaçäo no número de consultas por período, dependendo da divulgaçäo da existência do serviço, a média é de 1,5 consultas ao dia. Näo h preferência entre os sexos e o uso é näo profissional na maioria das perguntas. Questöes sobre drogas de abuso (inalantes e maconha) säo mais frequentes, havendo interesse na obtençäo de mais informaçöes sobre medicamentos prescritos (benzodiazepínicos e antidepressivos), tanto de açäo central como de outros tipos (drogas cardiovasculares e antimicrobianos). É pequeno o número de perguntas sobre cafeína, nicotina e alucinógenos

Effect of sodium valproate on the open-field behavior of rats

It has been reported that sodium valproate induces a morphine-like withdrawal syndrome in rats. The effects of acute or chronic treatment with sodium valproate on rat behavior was studied in the open-field test. Acute sodium valproate (320 mg/kg, intraperitoneally) decreases the freuqncy of, and the time spent in grooming even when not modifying locomotion, rearing or defecation (N=15), either 15 or 60 min after an acute treatment. This effect was not modified (n+10) by concomitant administration of morphine (2 mg/kg) or naloxone (1 mg/kg). Interruption of prolonged (30 days) valproate treatment with increasing doses of 40 to 320 mg/kg, by gavage, twice daily (N=10) did not modify raty behavior in the open-field, from the first to the fourtheenth day of th test. We conclude that the decreased novely-induced grooming does not depend on the opioid system and may be related to anti-anxiety effect of valproate

Inhibition of enteropathogenic Escherichia coli adherence to Hela cells by immune rabbit sera

We have studied the effect of immune rabbit sera on the localized (LA) and diffuse (DA) adherence to Hela cells of 10 enteropathogenic Escherichia coli (EPEC) strains belonging to serogroups 055, 086, 0111, 0119, and 0142. Anti-La1 serum, obtained by rabbit immunization with an E. coli strain harboring a cloned DNA fragment from an EPEC LA plasmid, strongly inhibited the adherence of all serogroups but one (0142). Similar results were obtained with anti-LA2 serum, which is anti-0111 serum absorbed with a non-adherence 0111:H-EPEC strain. In contrast, non-absorbed anti-055 and anti-0111 sera showed an inhibitory effect mainly on the adherence of homologous strains. Except for one experiment diffuse adherence was not inhibited by any antiserum used. The inhibitory effect of immune sera on localized adhere3nce does not seem to be correlated with plasmid curing sinceadherence plasmid pMS49 proved to be stable a after treatment with anti-055 and anti-0111 sera. The cross-inhibition of adherence by anti-LA sera suggests that localized adherence-related adhesions of the 0.55, 0.86, 0111, and 0119 strains share similar antigens

Effects of phenylethylamine on rat locomotor behavior and avoidance learning

1. The effects of ß-phenylethylamine (PEA) alone and in association with caroxazone, a potent inhibitor of monoamine oxidase B (MAO B), on the activity and long-term memory in the wheel-shaped activity monitor and on fixed-interval two-way avoidance acquisition were studied in rats. In a separate study, we determined the effects of PEA and of d-amphetamine on the variable-internal two-way avoidance acquisition. 2. The action of PEA was markedly different from that of aplhetamine in several aspects. The stimulating effects of PEA in the wheel-shaped activity monitor were of a more subtle nature than those of amphetamine and in the variable-interval two-way avoidance acquisition PEA had no effect, while amphetamine improved performance. 3. PEA did not induce an increase in path-choice stereotypy, but caroxazone did. The absence of any caroxazone-session interaction effects on the path interation frequency suggested that there were no long-term memory effects. 4. In the fixed-interval two-way avoidance acquisition experiments, PEA increased the avoidance responses of tats while caroxazone had no effect. The association of the two drugs did not potenciate either

Diagnóstico de fenilquetonuria en Chile / Phenylketonuria: late diagnosis

Se presentan las características clínicas y bioquímicas de 4 niños PKU diagnosticados tardíamente, a una edad promedio de 3 años 11 meses. Se enfatiza la importancia de hacer un diagnóstico y tratamiento oportuno, de modo de prevenir la aparición de retardo mental. Se plantea la necesidad de desarrollar un programa de búsqueda masiva para la detección de PKU en el período neonatal en nuestro país