Cocaine effects on mouse incentive-learning and human addiction are linked to alpha 2 subunit-containing GABA(A) receptors

Because GABA(A) receptors containing alpha 2 subunits are highly represented in areas of the brain, such as nucleus accumbens (NAcc), frontal cortex, and amygdala, regions intimately involved in signaling motivation and reward, we hypothesized that manipulations of this receptor subtype would influence processing of rewards. Voltage-clamp recordings from NAcc medium spiny neurons of mice with alpha 2 gene deletion showed reduced synaptic GABA(A) receptor-mediated responses. Behaviorally, the deletion abolished cocaine`s ability to potentiate behaviors conditioned to rewards (conditioned reinforcement), and to support behavioral sensitization. In mice with a point mutation in the benzodiazepine binding pocket of alpha 2-GABA(A) receptors (alpha 2H101R), GABAergic neurotransmission in medium spiny neurons was identical to that of WT (i.e., the mutation was silent), but importantly, receptor function was now facilitated by the atypical benzodiazepine Ro 15-4513 (ethyl 8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5-a] [1,4] benzodiazepine-3-carboxylate). In alpha 2H101R, but not WT mice, Ro 15-4513 administered directly into the NAcc-stimulated locomotor activity, and when given systemically and repeatedly, induced behavioral sensitization. These data indicate that activation of alpha 2-GABA(A) receptors (most likely in NAcc) is both necessary and sufficient for behavioral sensitization. Consistent with a role of these receptors in addiction, we found specific markers and haplotypes of the GABRA2 gene to be associated with human cocaine addiction.

Compulsive features in behavioural addictions: the case of pathological gambling

Aims To describe, in the context of DSM-V, how a focus on addiction and compulsion is emerging in the consideration of pathological gambling (PG). Methods A systematic literature review of evidence for the proposed re-classification of PG as an addiction. Results Findings include: (i) phenomenological models of addiction highlighting a motivational shift from impulsivity to compulsivity associated with a protracted withdrawal syndrome and blurring of the ego-syntonic/ego-dystonic dichotomy; (ii) common neurotransmitter (dopamine, serotonin) contributions to PG and substance use disorders (SUDs); (iii) neuroimaging support for shared neurocircuitries between behavioural and substance addictions and differences between obsessivecompulsive disorder (OCD), impulse control disorders (ICDs) and SUDs; (iv) genetic findings more closely related to endophenotypic constructs such as compulsivity and impulsivity than to psychiatric disorders; (v) psychological measures such as harm avoidance identifying a closer association between SUDs and PG than with OCD; (vi) community and pharmacotherapeutic trials data supporting a closer association between SUDs and PG than with OCD. Adapted behavioural therapies, such as exposure therapy, appear applicable to OCD, PG or SUDs, suggesting some commonalities across disorders. Conclusions PG shares more similarities with SUDs than with OCD. Similar to the investigation of impulsivity, studies of compulsivity hold promising insights concerning the course, differential diagnosis and treatment of PG, SUDs, and OCD.

Role of Two Clusters of Male Alcoholics in Treatment Retention

Aims: This study aimed to classify alcohol-dependent outpatients on the basis of clinical factors and to verify if the resulting types show different treatment retention. Methods: The sample comprised 332 alcoholics that were enrolled in three different pharmacological trials carried out at Sao Paulo University, Brazil. Based on four clinical factors problem drinking onset age, familial alcoholism, alcohol dependence severity, and depression - K-means cluster analysis was performed by using the average silhouette width to determine the number of clusters. A direct logistic regression was performed to analyze the influence of clusters, medication groups, and Alcoholics Anonymous ( AA) attendance in treatment retention. Results: Two clusters were delineated. The cluster characterized by earlier onset age, more familial alcoholism, higher alcoholism severity, and less depression symptoms showed a higher chance of discontinuing the treatment, independently of medications used and AA attendance. Participation in AA was significantly related to treatment retention. Discussion: Health services should broaden the scope of services offered to meet heterogeneous needs of clients, and identify treatment practices and therapists which improve retention. Information about patients' characteristics linked to dropout should be used to make treatment programs more responsive and attractive, combining pharmacological agents with more intensive and diversified psychosocial interventions. Copyright (C) 2012 S. Karger AG, Basel

Antinociception induced by acute oral administration of sweet substance in young and adult rodents: The role of endogenous opioid peptides chemical mediators and mu(1)-opioid receptors

The present work aimed to investigate the effects of acute sucrose treatment on the perception of painful stimuli. Specifically, we sought to determine the involvement of the endogenous opioid peptide-mediated system as well as the role of the mu(1)-opioid receptor in antinociception organisation induced by acute sucrose intake. Nociception was assessed with the tail-flick test in rats (75, 150 and 250 g) of different ages acutely pre-treated with 500 mu L. of a sucrose solution (25, 50, 150 and 250 g/L) or tap water. Young and Adult rats (250 g) showed antinociception after treatment with 50 g/L (during 5 min) and 150 g/L and 250 g/L (during 20 min) sucrose solutions. Surprisingly, this antinociception was more consistent in mature adult rodents than in pups. To evaluate the role of opioid systems, mature adult rodents were pre-treated with different doses (0.25, 1 or 4mg/kg) of the non-selective opioid receptor antagonist naloxone, the selective pi-opioid receptor antagonist naloxonazine or vehicle followed by 250 g/L sucrose solution treatment. Sucrose-induced antinociception was reduced by pre-treatment with both naloxone and naloxonazine. The present findings suggest that sweet substance-induced hypo-analgesia is augmented by increasing sucrose concentrations in young and adult rodents. Acute oral sucrose treatment inhibits pain in laboratory animal by mediating endogenous opioid peptide and mu(1)-opioid receptor actions. (C) 2011 Elsevier Inc. All rights reserved.

ADOLESCENCE AND DRUG USE THROUGH THE LENS OF PSYCHOANALYSIS: SUFFERING AND ECSTASY IN THE PASSAGE

ADOLESCENCE AND DRUG USE THROUGH THE LENS OF PSYCHOANALYSIS: SUFFERING AND ECSTASY IN THE PASSAGE The purpose of this study is to reflect upon the psychological factors of adolescent drug addiction according to a psychoanalytic perspective. First we consider adolescence as a social-historical category and then we discuss the psychoanalytic understanding of the adolescent transition. This theoretical path builds the approach that considers drug use as a phenomenon that serves as a passage ritual to contemporary adolescence. This phenomenon is modulated by the drive organization, which determines how the individual will take ownership of the use of psychoactive substances. We conclude that the substance use may function as a buffer-object, activated to deal with the structural fragility of the contemporary affective bonds.

Environmental enrichment blocks ethanol-induced locomotor sensitization and decreases BDNF levels in the prefrontal cortex in mice

The use of addictive drugs can lead to long-term neuroplastic changes in the brain, including behavioral sensitization, a phenomenon related to addiction. Environmental enrichment (EE) is a strategy used to study the effect of environment on the response to several manipulations, including treatment with addictive drugs. Brain-derived neurotrophic factor (BDNF) has been associated with behaviors related to ethanol addiction. The aim of the present study was to evaluate the effects of EE on ethanol-induced behavioral sensitization and BDNF expression. Mice were exposed to EE and then repeatedly treated with a low dose (1.8 g/kg) of ethanol. Another group of mice was first subjected to repeated ethanol treatment according to the behavioral sensitization protocol and then exposed to EE. Environmental enrichment prevented the development of ethanol-induced behavioral sensitization and blocked behavioral sensitization in sensitized mice. Both repeated ethanol and EE decreased BDNF levels in the prefrontal cortex but not in the hippocampus. However, BDNF levels were lower in ethanol-treated mice exposed to EE. These findings suggest that EE can act on the mechanisms implicated in behavioral sensitization, a model for drug-induced neuroplasticity and relapse. Additionally, EE alters BDNF levels, which regulate addiction-related behaviors.

Psychosocial and clinical predictors of retention in outpatient alcoholism treatment

Objective: One of the factors associated with low rates of compliance in the treatment for alcoholism seems to be the intensity of craving for alcohol. This study aimed to evaluate the associations between alcohol craving and biopsychosocial addiction model-related variables and to verify whether these variables could predict treatment retention. Methods: The sample consisted of 257 male alcoholics who were enrolled in two different pharmacological trials conducted at the Universidade de Sao Paulo in Brazil. Based on four factors measured at baseline - biological (age, race, and family alcoholism), psychiatric (depression symptoms), social (financial and marital status), and addiction (craving intensity, severity of alcohol dependence, smoking status, drinking history, preferential beverage, daily intake of alcohol before treatment) - direct logistic regression was performed to analyze these factors' influence on treatment retention after controlling for medication groups and AA attendance. Results: Increasing age, participation in Alcoholics Anonymous groups, and beer preference among drinkers were independently associated with higher treatment retention. Conversely, higher scores for depression increased dropout rates. Conclusion: Health services should identify the treatment practices and therapists that improve retention. Information about patients' characteristics linked to dropouts should be studied to render treatment programs more responsive and attractive, combining pharmacological agents with more intensive and diversified psychosocial interventions.

Effect of liposome-encapsulated nisin and bacteriocin-like substance P34 on Listeria monocytogenes growth in Minas frescal cheese

The efficacy of liposome-encapsulated nisin and bacteriocin-like substance (BLS) P34 to control growth of Listeria monocytogenes in Minas frescal cheese was investigated. Nisin and BLS P34 were encapsulated in partially purified soybean phosphatidylcholine (PC-1) and PC-1-cholesterol (7:3) liposomes. PC-1 nanovesicles were previously characterized. PC-1-cholesterol encapsulated nisin and BLS P34 presented, respectively, 218 nm and 158 nm diameters, zeta potential of -64 mV and -53 mV, and entrapment efficiency of 88.9% and 100%. All treatments reduced the population of L monocytogenes compared to the control during 21 days of storage of Minas frescal cheese at 7 degrees C. However, nisin and BLS P34 encapsulated in PC-1-cholesterol liposomes were less efficient in controlling L monocytogenes growth in comparison with free and PC-1 liposome-encapsulated bacteriocins. The highest inhibitory effect was observed for nisin and BLS P34 encapsulated in PC-1 liposomes after 10 days of storage of the product The encapsulation of bacteriocins in liposomes of partially purified soybean phosphatidylcholine may be a promising technology for the control of food-borne pathogens in cheeses. (C) 2012 Elsevier B.V. All rights reserved.

Avaliação da equivalência semântica e consistência interna de uma versão em português do Internet Addiction Test (IAT)

OBJETIVO: Este estudo teve por objetivo a adaptação transcultural do Internet Addiction Test (IAT) para o idioma português. MÉTODOS: O trabalho consistiu em cinco etapas: (1) tradução; (2) retradução; (3) revisão técnica e avaliação da equivalência semântica por profissionais da área; (4) avaliação do instrumento por uma amostra de estudantes, avaliando-se o seu grau de compreensão; e (5) análise da consistência interna por meio do coeficiente alfa de Cronbach. RESULTADOS: O instrumento foi traduzido e adaptado para o idioma português, demonstrando ser facilmente compreendido e apresentando valor de consistência interna de 0,85. CONCLUSÃO: O instrumento encontra-se traduzido e adaptado para o português e apresenta consistência interna satisfatória. São necessárias análises de equivalência de mensuração e reprodutibilidade.

Using selected scenes from Brazilian films to teach about substance use disorders, within medical education

CONTEXT AND OBJECTIVES: Themes like alcohol and drug abuse, relationship difficulties, psychoses, autism and personality dissociation disorders have been widely used in films. Psychiatry and psychiatric conditions in various cultural settings are increasingly taught using films. Many articles on cinema and psychiatry have been published but none have presented any methodology on how to select material. Here, the authors look at the portrayal of abusive use of alcohol and drugs during the Brazilian cinema revival period (1994 to 2008). DESIGN AND SETTING: Qualitative study at two universities in the state of São Paulo. METHODS: Scenes were selected from films available at rental stores and were analyzed using a specifically designed protocol. We assessed how realistic these scenes were and their applicability for teaching. One author selected 70 scenes from 50 films (graded for realism and teaching applicability > 8). These were then rated by another two judges. Rating differences among the three judges were assessed using nonparametric tests (P < 0.001). Scenes with high scores (> 8) were defined as "quality scenes". RESULTS: Thirty-nine scenes from 27 films were identified as "quality scenes". Alcohol, cannabis, cocaine, hallucinogens and inhalants were included in these. Signs and symptoms of intoxication, abusive/harmful use and dependence were shown. CONCLUSIONS: We have produced rich teaching material for discussing psychopathology relating to alcohol and drug use that can be used both at undergraduate and at postgraduate level. Moreover, it could be seen that certain drug use behavioral patterns are deeply rooted in some Brazilian films and groups.