Helena Maria Tannhauser Barros

Ethopharmacology of imipramine in the forced-swimming test: gender differences

Most of the pre-clinical tests used to assay the efficacy of prospective new agents are done with male experimental animals. In this case, a large part of the population is disregarded as is the interaction of the new agents effects with female hormonal fluctuations. The present study reviews the technical procedures characteristic for the forced-swimming test and the behavioral outcome induced by the testing procedure in males. It also compares the anti-immobility effects of the classic antidepressant imipramine (IMI) in male and female rats using a detailed behavioral scoring. Female rats had vaginal smears done before the beginning of the behavioral testing and were administered with three doses 24 h, 5 h and 1 h before the retest, as were male rats. Tests were videotape-recorded for analysis of the frequency and duration of the behaviors during forced-swimming. Male rats spend around 50% of the time immobile during the retest. There was a significant, dose-dependent decrease in immobility duration and a decrease in head-shakes of male rats treated with IMI. Both active behaviors of climbing and swimming were equally enhanced by the tricyclic antidepressant, climbing behavior comprising 75% of the mobile behaviors. Females showed much lower immobility duration and head-shake frequency during the forced-swimming than males and spent longer periods in mobile behaviors. Imipramine only decreases immobility frequency and head-shakes of females, and increases the escape-type behavior of climbing, decreasing swimming in the middle of the tank. This effect is more noticeable during estrus and proestrus. These results demonstrate the main behavioral differences between males and females in the forced-swimming test. It also elucidates that the effects of imipramine are measurable in males using the duration of the behaviors, while the frequencies of behaviors are modified in females treated with imipramine.

O abuso de esteróides anabólico-androgênicos em atletismo

, conforme detectado em estudos internacionais.Os EAA chegam ao Brasil provenientes dos Es-tados Unidos, Alemanha, Espanha, Franca, Ar-gentina, Uruguai ou Paraguai com muita facilida-de e sem qualquer tipo de fiscalizacao. De acordocom a Secretaria de Vigilância Sanitaria, ate hojenao ha qualquer disposicao legal ou regulamentarque imponha controle de comercializacao e uso detais substâncias, ou seja, o Brasil nao tem legisla-cao especifica no controle sobre anabolizantes

Prevalência do consumo de drogas na FEBEM, Porto Alegre

OBJECTIVE This study aimed to determine the prevalence of drug use among institutionalized children and adolescents; to assess the degree of associated use of illicit drugs with alcohol and tobacco; and to determine which is the gateway drug to illicit drug use. METHODS A cross-sectional study was carried out in the Fundação Estadual do Bem-Estar do Menor, in Porto Alegre (FEBEM) Southern Brazil. A questionnaire developed by the World Health Organization to determine prevalence off drug use was answered anonymously by a population of literate minors who were in FEBEM because of delinquency or due to social risk. The analysis aimed to describe the frequency of use of each drug and relate it to gender, age of beginning, and reason of institutionalization. RESULTS A total of 382 participants answered the questionnaire. The substances most frequently used on an experimental basis were: alcohol (81,3%), tobacco (76,8%), marijuana (69,2%), cocaine (54,6%), inhalants (49,2%), anxiolytic drugs (13,4%), hallucinogens (8,4%), amphetamines (6,5%) and barbiturates (2,4%). Overall, around 80% of the respondents reported having used some illicit drug at least once in the past. Licit drugs, like alcohol and tobacco, were used mainly by males, while medicines were used mostly by females. Adolescents with delinquency records showed a significantly higher frequency of alcohol, marijuana, cocaine, and solvent use. The mean age of beginning was under 12 years for alcohol and tobacco use, under 13 years for marijuana and inhalants, and under 14 years for cocaine. Concomitant use of illicit and licit drugs was found to be high in this population. CONCLUSIONS A high prevalence of precocious drug use was found among institutionalized children and adolescent, with alcohol and tobacco being used earlier than illicit drugs. Delinquent males were more likely to have used illicit drugs.

Comparison of behavioral effects of moclobemide and deprenyl during forced swimming.

The present study compared the antiimmobility effects of l-deprenyl (DEP) and moclobemide (MOC) to the classic antidepressant imipramine (IMI), using an ethological approach. To investigate the degree of MAO-B inhibition by DEP and MOC, combination of treatments of ineffective doses of phenylethylamine (PHEA) with DEP or with MOC were administered in three doses before immobility was tested in the forced-swimming paradigm. Tests were videotape recorded for analysis of the frequency and duration of the behaviors during the procedure. There was a significant, dose-dependent decrease in immobility duration and an increase in mobility duration of rats treated with IMI. Both active behaviors of climbing and swimming were equally enhanced by the tricyclic antidepressant, climbing behavior composing 75% of the mobile behaviors. The intermediate doses of the MAOIs tested, DEP 0.25 mg/kg and MOC 30 mg/kg, decreased immobility and increased mobility. The antiimmobility effect of DEP was due to longer climbing behavior while MOC enhanced swimming duration. No behavioral changes were seen with the administration of the lower and higher doses of the MAOI. Potentiation of the antiimmobility effects was observed when ineffective doses of PHEA and of DEP or MOC were administered in combination. Differences between the MAO inhibitors on the active behaviors were also observed when administered with PHEA; DEP and PHEA significantly increased climbing and MOC and PHEA increased swimming. This preclinical evaluation of selective MAO inhibitors indicates that both MAO-A and MAO-B inhibitors have antidepressant effects. However, to clearly demonstrate that these antiimmobility effects are a consequence of increased brain concentrations of any one of the several monoamines implicated in the mechanism of action of DEP or MOC should be the subject of future studies.

Lower in vivo brain extracellular GABA concentration in diabetic rats during forced swimming.

Diabetic rats are more immobile during the forced-swimming test (FST) and GABAergic drugs reverse this behavior. We investigated if there is in vivo changes of GABA levels of diabetic rats during the FST. In vivo basal striatal GABA levels of streptozotocin diabetic rats are similar to non-diabetic rats. Non-diabetic rats presented a significant increase in GABA levels after the FST while the increase was delayed and lower in diabetic rats. These results suggest that diabetes may change GABA homeostasis and modify behavioral responses in an animal model of depression.

Brief Motivational Intervention and telemedicine: a new perspective of treatment to marijuana users.

The main purpose of this study was to evaluate the telephone Brief Motivational Intervention (BMI) efficacy in marijuana consumption cessation. A clinical trial was performed on Brazilian citizens, who were randomly divided into experimental (BMI) and minimal intervention (reference material) treatment groups; the study involved 524 participants who were monitored for 6 months. In addition, the data was collected by a free-service call center; both marijuana consumption and level of motivation for behavior change were evaluated, based on the telephone service offered. The proportion of abstainers in the BMI group was significantly greater than in the control group: 73% of the individuals in the BMI group were abstainers. In the control group, 59% of them ceased on using marijuana. The ratio of probability for marijuana cessation was 1.6 times higher in the BMI group. There was no significant difference on the motivation for behavior change in both groups. The collected data demonstrated the telephone BMIs positive efficacy in marijuana consumption cessation.

A violência comunitária e o abuso de álcool entre adolescentes: comparação entre sexos

OBJECTIVE To verify whether there is an association between victimization and alcohol use among boys and girls in Porto Alegre, RS, Brazil. METHODS This was a cross-sectional study of students from public schools, aged 10 to 19 years, from the fifth grade of primary education to the third grade of secondary education, selected by two-stage cluster sampling, defined by the socioeconomic characteristics of the neighborhood in which each school is located and by school class. Data collection was by means of a questionnaire which was completed anonymously and voluntarily. RESULTS Fifty-four percent of the older adolescent boys (aged 14-19) drank alcohol, compared to 17% of the younger adolescent boys (10-13), as did 58% of the older adolescent girls and 19% of the younger adolescent girls. Fifty-seven percent of the students had suffered severe victimization, and 53% had suffered moderate victimization. When the samples were separated by sex, it was observed that boys and girls who drank alcohol reported 2.6 and 1.8 times more severe victimization respectively, while alcohol was associated with 3.1 and 2.5 times greater prevalence of moderate victimization, among boys and girls respectively. When episodes of drunkenness were analyzed, it was observed that adolescents got drunk more than pre-adolescents and that exposure to violence exhibited an increased association with drunkenness. Thirty-two percent of the boys (prevalence ratio, PR = 4.4; 95%CI 2.6-7.3) and 22% of the girls (PR = 2.2; 95%CI 1.2-4.1) who had been the victims of severe violence reported being drunk at least once. CONCLUSIONS Adolescents of both sexes who consume more alcohol are at greater risk of suffering community violence.

Oxidative stress parameters in diabetic rats submitted to forced swimming test: the clonazepam effect

Diabetes-associated depression may occur due to changes in the quality of life imposed by treatment, or may be a consequence of the biochemical changes accompanying the disease. We evaluated the oxidative stress from diabetic animals submitted to an experimental model of depression and the effects of clonazepam. Male Wistar rats were induced to diabetes with streptozotocin and submitted to forced swimming test. Clonazepam was administered 24, 5 and 1 h before test. The animals were sacrificed by decapitation, and plasma and erythrocytes were separated, as well as hippocampus, cortex and striatum. Reactive species of thiobarbituric acid (TBARS) and total antioxidant reactivity (TAR) as well as antioxidant enzyme activities catalase (CAT) and superoxide dismutase (SOD) were evaluated. Results showed a significant increase of TBARS and a significant decrease of TAR in plasma from diabetic animals, which was altered by clonazepam. There were no effects of CAT and SOD activities in erythrocytes from tested animals. The results observed in hippocampus showed a significant increase of TBARS from diabetic rats, altered by clonazepam, and no one alteration was verified in TAR. The significant increase of TBARS and the significant decrease of TAR in cortex from diabetic rats were not altered by clonazepam administration. There were no alterations of TBARS and TAR in striatum from tested animals. Besides, clonazepam reverses the immobility in diabetic rats. Considering the action of clonazepam, it is suggested that it could be an alternative therapeutic for depression to diabetic patients, once it could give a protection against free radicals.

Protein and lipid oxidative damage in streptozotocin-induced diabetic rats submitted to forced swimming test: the insulin and clonazepam effect

Diabetes may modify central nervous system functions and is associated with moderate cognitive deficits and changes in the brain, a condition that may be referred to as diabetic encephalopathy. The prevalence of depression in diabetic patients is higher than in the general population, and clonazepam is being used to treat this complication. Oxidative stress may play a role in the development of diabetes complications. We investigated oxidative stress parameters in streptozotocin-induced diabetic rats submitted to forced swimming test (STZ) and evaluated the effect of insulin (STZ-INS) and/or clonazepam (STZ-CNZ and STZ-INS-CNZ) acute treatment on these animal model. Oxidative damage to proteins measured as carbonyl content in plasma was significantly increased in STZ group compared to STZ treated groups. Malondialdehyde plasma levels were significantly reduced in STZ-INS and STZ-INS-CNZ groups when compared to STZ rats, being significantly reduced in STZ-INS-CNZ than STZ-INS rats. The activities of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase showed no significant differences among all groups of animals. These findings showed that protein and lipid damage occurs in this diabetes/depression animal model and that the associated treatment of insulin and clonazepam is capable to protect against oxidative damage in this experimental model.

Influence of handling or aversive stimulation during rats' neonatal or adolescence periods on oral cocaine self-administration and cocaine withdrawal

Adverse early life events may influence vulnerability for drug intake. The influence of handling or aversive stimulation during neonatal or adolescent periods on adult cocaine oral self-administration and withdrawal were investigated. Neonatal or adolescent rats were exposed to a modified unpredictable stress paradigm or handling for 10 days. When adults, oral cocaine was offered through the two-bottle choice paradigm for 30 days. Rats were submitted to the forced swimming test after cocaine withdrawal. Overall, there was a significant increase of cocaine choice throughout the days of cocaine consumption and an interaction between interventions and cocaine daily choice. Control rats started cocaine intake at a lower level and increased cocaine choice over time, while animals submitted to neonatal interventions started cocaine intake at higher levels of choice, with less increase in cocaine intake during the period of cocaine exposure. Rats receiving aversive stimulation during adolescence also started taking cocaine solution at higher levels. Significantly higher immobility duration and shorter latency to immobility during the forced swimming were detected in these same adolescents that received unpredictable stress, when compared to the control or handled rats, while there was no difference for rats stimulated neonatally. Therefore, early life events increase initial preference for cocaine and promote changes in its abuse pattern, according to the intensity of the event and the age of the individual at the time of the event. Moreover, adverse experiences during adolescence, but not in neonatal phases, increase the vulnerability to depressive-like behaviors during cocaine withdrawal of adult rats.