Booster effects and mechanisms of web-based personalised normative feedback alcohol intervention for college students: A pragmatic randomised controlled trial.

BACKGROUND: To evaluate the effects of booster and no booster versions of web-based alcohol Personalised Normative Feedback (PNF) and whether descriptive norms mediated and/or participant motivation moderated the effectiveness of the intervention in real world conditions (i.e. no financial incentives). METHODS: Pragmatic randomised controlled trial with 1-, 3-, and 6-month assessments. Brazilian college students reporting alcohol use in the last 12 months (N=931) were recruited from May/2020 to December/2022 and allocated to 1) No booster/single PNF(S-PNF); 2) Booster/multiple PNF(M-PNF); or 3) Assessment-only control. We applied Helmert coding [1: Any intervention (S-PNF or M-PNF) vs. Control; and 2: S-PNF vs. M-PNF]. PRIMARY OUTCOMES: typical number of drinks/week and maximum number of drinks/week; secondary outcomes: drinking frequency and number of consequences. Three-months assessment was the primary interval. Descriptive norms were tested as mediator. Interest, importance, and readiness to change were examined as moderators. RESULTS: Compared to control, any intervention did not influence primary outcomes at 3-months or 6-months, but did at 1-month, when reduced typical drinking (IRR:0.77, 95%CI:0.66;0.90) and maximum number of drinks (IRR:0.69, 95%CI:0.58;0.82). There was an intervention effect on the consequences at 3-months. No differences were observed between S-PNF and M-PNF. No mediation effects were found at 3-months. At 6-months, there was an indirect effect on typical drinking through norms at 3-months (b=-0.82, 95%CI:-2.03;-0.12) and effects on maximum drinks through norms at 1-month (b=-0.54, 95%CI:-1.65;-0.02). No support for moderation was found. CONCLUSIONS: Intervention reduced alcohol drinking at 1 month only and was not effective thereafter. Mechanisms of effect remain unclear.

Mediational Analyses of the Effects of Social Behaviour and Network Therapy on Alcohol Use.

INTRODUCTION: Social behaviour and network therapy involves an active participation of the practitioner in recruiting a supportive network to change the client's alcohol use. Despite achieving beneficial effects on alcohol consumption, its possible mechanisms of change are a relatively under-studied topic compared to those of other alcohol treatment interventions. This study aimed to explore therapist skills through which social behaviour and network therapy may achieve effects on alcohol consumption in comparison with motivational enhancement therapy. METHODS: This study was secondary analysis of data from the UK Alcohol Treatment Trial, a multicentre, pragmatic, randomized controlled trial. The sample comprised 376 participants randomized to motivational enhancement therapy or social behaviour and network therapy. We used the UK Alcohol Treatment Trial Process Rating Scale to assess therapist skills. Outcomes drinks per drinking day and percentage of days abstinent were assessed 12 months after treatment initiation. Analyses were conducted in a simple mediation framework. RESULTS: Therapist skills score (combining frequency and quality) for involving others in behaviour change mediated social behaviour and network therapy effects on percentage of days abstinent (b = 0.06, 95% CI: 0.02; 0.10, p = 0.01). The frequency with which therapists acted as an active agent for change also mediated the effects of social behaviour and network therapy on percentage of days abstinent (b = 0.03, 95% CI: 0.003; 0.05, p = 0.03). The frequency with which the therapist stressed social support as a key factor in achieving change unexpectedly mediated an increase in drinks per drinking day (b = 0.10, 95% CI: 0.01; 0.18, p = 0.02). The two latter mediation effects were not sustained when quality was considered. All other indirect effects tested were non-significant. DISCUSSION/CONCLUSIONS: How social behaviour and network therapy exerts effects on alcohol outcomes is not yet well understood and in this study was not attributable to observed ratings of therapist treatment-specific skills. Therapist skill in planning the involvement of others during treatment, however, warrants further study. We suggest that the present findings should be regarded as hypothesis generating as it identifies specific targets for further investigation in alcohol treatment process studies.

Ethanol combined with energy drinks: Two decades of research in rodents.

Many studies raised concerns on alcoholic beverages consumption mixed with energy drinks (AmED), which can induce higher rates of binge drinking and earlier development of alcohol use disorders. After 20 years of research, few studies with laboratory animals have focused on the effects of this mixture and the neurobiological and pharmacological mechanisms underlying them. We found 16 articles on AmED administration to rodents evaluating its effects on voluntary consumption, locomotion, anxiety-like behavior, memory, influence on the onset time of seizures, biochemical and neurochemical measures. Some of these studies indicated energy drinks (ED) can alter the pattern of use and motivation to consume ethanol (EtOH); increase the expression of sensitization to EtOH stimulant effect and the proportion of sensitized mice; decrease the aversiveness of high concentrations of EtOH, among other effects. In addition AmED hastens the loss of righting reflex and its effects on memory are controversial. After acute administration no difference was found in blood ethanol concentration (BEC) of rodents which received EtOH with or without ED, but after 60 days of treatment, AmED group had lower BEC levels than EtOH group. Data on biochemical and neurochemical parameters after AmED are not consistent. Although the AmED group presented higher glucose levels than the EtOH group when drugs were administered by gavage, this was not observed in a self-administration protocol. AmED may induce higher kidney damage, higher levels of plasma urea, uric acid and creatinine when compared to EtOH. Chronic consumption of AmED causes an inflammatory response and oxidative stress, which may induce cell death in the cortex and hypothalamus of adult rats. These controversial results show that AmED diverse effects depend on sex, age and lineage of the animals, duration of the treatment and route of administration. Further research is necessary to evaluate the mechanisms underlying AmED biological effects.

Association between polymorphism in gene related to the dopamine circuit and motivations for drinking in patients with alcohol use disorder.

The development of alcohol use disorder (AUD) is influenced by genetic, psychological, and social factors. However, the identification of the load of each of these factors and the association between them is still debatable. This study aimed to explore the load of the association between AUD and polymorphisms in genes of the dopaminergic system, as well as with drinking triggers. The study comprised 227 inpatients with AUD and 174 controls. The pattern and motivations for drinking were evaluated using the Alcohol Use Disorders Identification Test (AUDIT) and the Inventory of Drinking Situations (IDS). Analyses of genetic variation in genes encoding dopaminergic were performed using next generation sequencing. We observed an significant association between a polymorphism in DDC (rs11575457) and AUD. Positive reinforcement factors as urges/temptations to drink and pleasant emotion, in isolation, were the significantly related elements to drinking. In addition, negative (physical discomfort) and positive reinforcement factors (testing personal control; pleasant time with others) significantly reinforced the interaction with DDC genetic variant for increased odds of an individual presenting AUD. These results indicated a complex relationship between the dopaminergic system and the drug-seeking behavior profiles.

Alcohol e-Help: study protocol for a web-based self-help program to reduce alcohol use in adults with drinking patterns considered harmful, hazardous or suggestive of dependence in middle-income countries.

BACKGROUND AND AIMS: Given the scarcity of alcohol prevention and alcohol use disorder treatments in many low and middle-income countries, the World Health Organization launched an e-health portal on alcohol and health that includes a Web-based self-help program. This paper presents the protocol for a multicentre randomized controlled trial (RCT) to test the efficacy of the internet-based self-help intervention to reduce alcohol use. DESIGN: Two-arm randomized controlled trial (RCT) with follow-up 6 months after randomization. SETTING: Community samples in middle-income countries. PARTICIPANTS: People aged 18+, with Alcohol Use Disorders Identification Test (AUDIT) scores of 8+ indicating hazardous alcohol consumption. INTERVENTION AND COMPARATOR: Offer of an internet-based self-help intervention, 'Alcohol e-Health', compared with a 'waiting list' control group. The intervention, adapted from a previous program with evidence of effectiveness in a high-income country, consists of modules to reduce or entirely stop drinking. MEASUREMENTS: The primary outcome measure is change in the Alcohol Use Disorders Identification Test (AUDIT) score assessed at 6-month follow-up. Secondary outcomes include self-reported the numbers of standard drinks and alcohol-free days in a typical week during the past 6 months, and cessation of harmful or hazardous drinking (AUDIT < 8). ANALYSIS: Data analysis will be by intention-to-treat, using analysis of covariance to test if program participants will experience a greater reduction in their AUDIT score than controls at follow-up. Secondary outcomes will be analysed by (generalized) linear mixed models. Complier average causal effect and baseline observations carried forward will be used in sensitivity analyses. COMMENTS: If the Alcohol e-Health program is found to be effective, the potential public health impact of its expansion into countries with underdeveloped alcohol prevention and alcohol use disorder treatment systems world-wide is considerable.

Country-wide distance training for delivery of screening and brief intervention for problematic substance use: A pilot evaluation of participant experiences and patient outcomes.

BACKGROUND: In this study, the authors evaluated if the 120-hour distance learning (DL) course SUPERA (an acronym in Portuguese meaning "System for detection of excessive use or dependence on psychoactive substances: brief Intervention, social reinsertion and follow-up") was an effective way to train health professionals and social workers to apply screening and brief intervention (SBI) for patients with substance use disorders. METHODS: In the first phase, 2420 health professionals or social workers, who had completed the course, answered an online survey about their use of the SBI. In the second phase, 25 of those professionals applied the ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) followed by a brief intervention (BI) to patients with substance use disorders. Three months after the SBI delivery, independent researchers followed up 79 patients who had received SBI, reapplying the ASSIST and a questionnaire to evaluate the patients'/clients' satisfaction with the intervention they received. RESULTS: In the first phase, it was found that most health professionals and social workers who completed the course applied the SBI in their work and felt very motivated to do it. In the second phase of the study, at a 3-month follow-up, most patients had significantly reduced their ASSIST scores in respect of alcohol and cocaine/crack in relation to their baseline levels. Those patients classified by their ASSIST score as "suggestive of dependence" presented a significant reduction in their scores regarding alcohol, tobacco, and cocaine/crack, whereas those classified as "at risk" presented a reduction in respect of alcohol problems only. Patients associated changes in their substance use with the SBI received. CONCLUSIONS: A reduction in substance use-related problems was associated with the SBI applied by the health professionals or social workers trained by the DL course SUPERA. Two significant limitations of this study were the small number of participants (professionals and patients in the follow-up) and the absence of a control group in the second phase of the study.

Web-based self-help intervention reduces alcohol consumption in both heavy-drinking and dependent alcohol users: A pilot study.

As part of a multicenter project supported by the World Health Organization, we developed a web-based intervention to reduce alcohol use and related problems. We evaluated the predictors of adherence to, and the outcomes of the intervention. Success was defined as a reduction in consumption to low risk levels or to <50% of the baseline levels of number of drinks. From the 32,401 people who accessed the site, 3389 registered and 929 completed the full Alcohol Use Disorders Identification Test (AUDIT), a necessary condition to be considered eligible to take part in the intervention. Based on their AUDIT scores, these participants were classified into: low risk users (LRU; n=319) harmful/hazardous users (HHU; n=298) or suggestive of dependence users (SDU; n=312). 29.1% of the registered users (LRU=42; HHU=90; SDU=82) completed the evaluation form at the end of the six-week period, and 63.5% reported low-risk drinking levels. We observed a significant reduction in alcohol consumption in the HHU (62.5%) and SDU (64.5%) groups in relation to baseline. One month after the intervention, in the follow-up, 94 users filled out the evaluation form, and their rate of success was similar to the one observed in the previous evaluation. Logistic regression analyses indicated that HHU participants presented higher adherence than LRU. Despite a relatively low adherence to the program, its good outcomes and low cost, as well as the high number of people that can be reached by a web-based intervention, suggest it has good cost-effectiveness.

Individual differences in ethanol locomotor sensitization are associated with dopamine D1 receptor intra-cellular signaling of DARPP-32 in the nucleus accumbens.

In mice there are clear individual differences in the development of behavioral sensitization to ethanol, a progressive potentiation of its psychomotor stimulant effect. Variability in the behavioral responses to ethanol has been associated with alcohol preference. Here we investigated if the functional hyperresponsiveness of D1 receptors observed in ethanol sensitized mice leads to an increased activation of DARPP-32, a central regulatory protein in medium spiny neurons, in the nucleus accumbens - a brain region known to play a role in drug reinforcement. Swiss Webster mice received ethanol (2.2 g/kg/day) or saline i.p. administrations for 21 days and were weekly evaluated regarding their locomotor activity. From those treated with ethanol, the 33% with the highest levels of locomotor activity were classified as "sensitized" and the 33% with the lowest levels as "non-sensitized". The latter presented similar locomotor levels to those of saline-treated mice. Different subgroups of mice received intra-accumbens administrations of saline and, 48 h later, SKF-38393, D1 receptor agonist 0.1 or 1 µg/side. Indeed, sensitized mice presented functional hyperresponsiveness of D1 receptors in the accumbens. Two weeks following the ethanol treatment, other subgroups received systemic saline or SKF 10 mg/kg, 20 min before the euthanasia. The nucleus accumbens were dissected for the Western Blot analyses of total DARPP-32 and phospho-Thr34-DARPP-32 expression. D1 receptor activation induced higher phospho-Thr34-DARPP-32 expression in sensitized mice than in non-sensitized or saline. The functionally hyperresponsiveness of D1 receptors in the nucleus accumbens is associated with an increased phospho-Thr34-DARPP-32 expression after D1 receptor activation. These data suggest that an enduring increase in the sensitivity of the dopamine D1 receptor intracellular pathway sensitivity represents a neurobiological correlate associated with the development of locomotor sensitization to ethanol.

Alpha1-adrenergic drugs affect the development and expression of ethanol-induced behavioral sensitization.

BACKGROUND: According to the incentive sensitization theory, addiction is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems. After repeated ethanol administration, some animals develop psychomotor sensitization, a phenomenon which occurs simultaneously with the incentive sensitization. Recent evidence suggests the involvement of norepinephrine (NE) in drug addiction, with a critical role in the ethanol reinforcing properties. In this study we evaluated the influence of an agonist (phenylephrine) and an antagonist (prazosin) of alpha1-adrenergic receptors on the development and expression of behavioral sensitization to ethanol. Male Swiss mice, previously treated with ethanol or saline, were challenged with the combined administration of ethanol (or saline) with alpha1-adrenergic drugs. Prazosin (0.1; 0.5 and 1.0 mg/kg) and phenylephrine (1.0 and 2.0 mg/kg) administration blocked the expression of behavioral sensitization to ethanol. In another set of experiments, mice treated with 0.5mg/kg of prazosin+ethanol did not present the development of behavioral sensitization. However, when challenged with ethanol alone, they showed the same sensitized levels of locomotor activity of those presented by mice previously treated with ethanol and saline. Phenylephrine (1.0 mg/kg) treatment did not affect the development of behavioral sensitization. Based on this data, we concluded that the alteration of alpha1-adrenergic receptors functioning, by the administration agonists or antagonists, affected the locomotor sensitization to the stimulant effect of ethanol, suggesting that the normal functioning of the noradrenergic system is essential to its development and expression.

Expression of behavioral sensitization to ethanol is increased by energy drink administration.

Alcohol abuse and dependence are important medical, social and economical problems, affecting millions of people. A relatively recent habit among young people is mixing alcohol with energy drinks (ED), in spite of the risks involved may be higher than those associated with alcohol consumption alone. The mixture of alcohol and energy drinks, both with stimulant properties, may alter the perception of intoxication and could lead individuals to believe they are less drunk and can drink more or for longer periods of time. In animals, the repeated administration of ethanol can lead to a progressive increase of the locomotor stimulant effect, known as behavioral sensitization, a drug-dependent behavioral plasticity associated with vulnerability to addiction. As well as for addiction, there are clear individual differences in the level of sensitization to ethanol among species and even among individuals from the same strain. The present study assessed how ED affects the expression of ethanol sensitization. Female mice chronically treated with ethanol (2.4 g/kg) were classified as low-sensitized or high-sensitized. Two days later, different groups of mice were submitted to saline+water, ethanol+water or ethanol+ED systemic challenges. As expected, only the high-sensitized group expressed clear sensitization after ethanol administration. However, the administration of ethanol+ED triggered the sensitization expression in the low-sensitized group. These data indicate that the combined use of ED and ethanol can potentiate the stimulant and, consequently, the reward effects of ethanol in previously treated mice. If a similar process occurs in human beings, the use of ED can increase the risk of developing alcohol abuse or dependence.

Relationship between stress symptoms and drug use among secondary students.

The aim of this study was to evaluate the relationship between drug use and four kinds of stress symptoms in 954 Brazilian students from the 6th to the 11th grades, in 4 public and 5 private schools in the city of Sao Paulo. Based on their answers to the Drug Use Screening Inventory (DUSI-R) and to the Stress Scale for Adolescents (SSA), we compared regular drug users with non/occasional drug users regarding the frequency of four kinds of stress symptoms (psychological, cognitive, physiological, interpersonal), and the period in which it happened. When compared to non/occasional drug users, regular drug users presented higher levels of psychological, cognitive and physiological symptoms of stress and these symptoms were in the most severe spectrum of severity (near to exhaustion and exhaustion). The association between drug use and stress was even stronger in the youngest age group (11 to 13 years old). Most of the regular drug users were 16 years old and over, from upper-middle class families, had poor family relationships and more academic problems. These results confirm the association between drug use and stress in adolescents and highlight the need for early screening and intervention in both drug use and stressful situations.

Avanços na psicometria: da Teoria Clássica dos Testes à Teoria de Resposta ao Item / Advances in psychometrics: from Classical Test Theory to Item Response Theory

No século XX, o desenvolvimento e avaliação das propriedades psicométricas dos testes se embasou principalmente na Teoria Clássica dos Testes (TCT). Muitos testes são longos e redundantes, com medidas influenciáveis pelas características da amostra dos indivíduos avaliados durante seu desenvolvimento, sendo algumas destas limitações consequências do uso da TCT. A Teoria de Resposta ao Item (TRI) surgiu como uma possível solução para algumas limitações da TCT, melhorando a qualidade da avaliação da estrutura dos testes. Neste texto comparamos criticamente as características da TCT e da TRI como métodos para avaliação das propriedades psicométricas dos testes. São discutidas as vantagens e limitações de cada método.(AU)

In the 20th century, development and evaluation of psychometric properties of tests was mainly based on the Classical Test Theory (CTT). Many tests are long and redundant, with measures influenced by the characteristics of the sample of the individuals being evaluated. Some of the limitations are a consequence of the use of the CTT. The Item Response Theory (IRT) has been proposed as a solution to some limitations of the CTT, improving the quality of assessment of the tests structure. In this paper we critically compare the characteristics of CTT and IRT methods in determining the psychometric properties of tests. We discuss the advantages and limitations of each method.(AU)

Avanços na psicometria: da Teoria Clássica dos Testes à Teoria de Resposta ao Item / Advances in psychometrics: from Classical Test Theory to Item Response Theory

No século XX, o desenvolvimento e avaliação das propriedades psicométricas dos testes se embasou principalmente na Teoria Clássica dos Testes (TCT). Muitos testes são longos e redundantes, com medidas influenciáveis pelas características da amostra dos indivíduos avaliados durante seu desenvolvimento, sendo algumas destas limitações consequências do uso da TCT. A Teoria de Resposta ao Item (TRI) surgiu como uma possível solução para algumas limitações da TCT, melhorando a qualidade da avaliação da estrutura dos testes. Neste texto comparamos criticamente as características da TCT e da TRI como métodos para avaliação das propriedades psicométricas dos testes. São discutidas as vantagens e limitações de cada método...

In the 20th century, development and evaluation of psychometric properties of tests was mainly based on the Classical Test Theory (CTT). Many tests are long and redundant, with measures influenced by the characteristics of the sample of the individuals being evaluated. Some of the limitations are a consequence of the use of the CTT. The Item Response Theory (IRT) has been proposed as a solution to some limitations of the CTT, improving the quality of assessment of the tests structure. In this paper we critically compare the characteristics of CTT and IRT methods in determining the psychometric properties of tests. We discuss the advantages and limitations of each method...

Behavioral sensitization to ethanol results in cross-sensitization to MK-801 but not to NMDA administered intra-accumbens.

In mice, repeated ethanol administration may induce behavioral sensitization - a process of progressive potentiation of its stimulant effects, associated with neuroadaptations in the brain reward system. Few studies have directly investigated the subsequent neuroadaptations in the nucleus accumbens (NAc), the central area of the brain reward system, after chronic ethanol administration. The goal of the present study was to analyze the involvement of accumbal glutamate NMDA receptors in the locomotion behavioral response to an NMDA agonist or to an NMDA antagonist in mice previously treated with ethanol. Swiss Albino mice received repeated daily administrations of 2.2 g/kg ethanol or saline for 21 days. According to their locomotor response on the last day of treatment, ethanol-treated mice were classified into sensitized or non-sensitized groups. They were then submitted to a surgical procedure to implement intra-NAc cannulae. After recovery, mice were challenged with intra-NAc administration of saline and, two days later, with NMDA (NMDA agonist) or MK-801 (NMDA antagonist), having their locomotor activity recorded for 1 h. The administration of NMDA induced similar locomotor behavior in all groups. On the other hand, the administration of 3 µg/side MK-801 induced a significant stimulant effect which was more prominent during the first 15 min in the sensitized group than in the non-sensitized or saline groups. Despite no effect of the agonist administration, only in sensitized mice did we observe cross-sensitization between repeated ethanol treatment and the intra-NAc administration of MK-801.

Accumbal dopamine D2 receptor function is associated with individual variability in ethanol behavioral sensitization.

Striatal dopamine D2 receptors have been implicated in the development of behavioral sensitization after repeated exposure to drugs of abuse. There are clear individual differences in the level of sensitization to ethanol among species and even among individuals from the same strain. Albino Swiss mice treated with ethanol (2.2 g/kg) have been shown to present clear variations in the development of sensitization. While some mice developed ethanol (EtOH) induced sensitization, others did not. This variability was associated with differences in D2 dopaminergic receptor binding. In the present study, we evaluated the functional relevance of dopamine D2 receptor by measuring, in sensitized and non-sensitized mice, the locomotor response to a D2 receptor agonist (quinpirole, 0.5 and 2.0 mg/kg i.p. or 0.01 and 0.2 µg/side intra-accumbens) or antagonist (sulpiride, 10 or 50 mg/kg i.p. or 0.02 µg/side intra-accumbens + ethanol i.p.). Whereas the systemic administration of quinpirole decreased locomotor activity in a similar way in all the groups, intra-nucleus accumbens (NAc) administration induced significantly higher locomotor stimulation in the sensitized group alone. Our data show that functionally hyperresponsive D2 receptors are present in the NAcs of sensitized but not non-sensitized mice, suggesting that this could be a biomarker of behavioral sensitization. Furthermore, i.p. administration of sulpiride blocked the expression of sensitization in the sensitized group, and intra-NAc administration attenuated it, indicating that the activation of accumbal D2 receptors is essential for the expression of EtOH behavioral sensitization. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Nucleus accumbens dopamine D1 receptors regulate the expression of ethanol-induced behavioural sensitization.

Repeated ethanol administration may induce behavioural sensitization, defined as a progressive potentiation of locomotor stimulant effects. This process is associated with neuroadaptations in the mesolimbic pathway and the nucleus accumbens. The aim of the present study was to analyse dopamine D1 receptor (D1R) participation in locomotor response to an agonist and an antagonist of the D1R in mice with different levels of sensitization to ethanol. In three separate experiments, mice received administrations of 2.2 g/kg ethanol or saline every other day for 10 d. According to their locomotor response on the last day, ethanol-treated animals were classified into two groups: sensitized or non-sensitized. After the treatment, mice were challenged with 4 or 8 mg/kg SKF-38393 (i.p.), a D1R agonist (expt 1); or with 0.01 or 0.1 mg/kg SCH-23390 (i.p.), a D1R antagonist, followed by 2.2 g/kg ethanol (i.p.) administration (expt 2). In expt 3, mice were challenged with intra-accumbens (intra-NAc) SKF-38393 (1 µg/side, in 0.2 µl), and with intra-NAc SCH-23390 (3 µg/side, in 0.2 µl) followed by 2.2 g/kg ethanol (i.p.). Although the i.p. administration of SKF-38393 did not affect the locomotion of mice, the intra-NAc administration of SKF-38393 significantly increased the locomotor activity in sensitized mice, suggesting that sensitized mice present functionally hyperresponsive D1Rs in the NAc. Both i.p. and intra-NAc administration of SCH-23390 blocked the expression of ethanol sensitization, suggesting that the activation of NAc D1Rs seems to be essential for the expression of ethanol sensitization.

Disulfiram impairs the development of behavioural sensitization to the stimulant effect of ethanol.

BACKGROUND: Although disulfiram has been used in the treatment of alcoholism due to the unpleasant sensations its concomitant ingestion with ethanol provokes, some patients reported stimulant effects after its ingestion. This issue has not been addressed in studies with animals. In mice, the stimulant effect of ethanol has been associated with increased locomotor activity and behavioural sensitization. This study sought to analyze the influence of disulfiram on the development of behavioural sensitization to the stimulant effect of ethanol. METHODS: Male Swiss mice pre-treated with vehicle or disulfiram (15 mg/kg) received saline or ethanol (2.0 g/kg) every other day, for 5 days. Forty-eight hours afterwards mice were challenged with Saline, and 48 h later they received Disulfiram, or Disulfiram+Ethanol or Ethanol. RESULTS: The co-administration of disulfiram (15 mg/kg) blocked the development of behavioural sensitization induced by ethanol (2.0 g/kg). Although the acute administration of disulfiram did not alter the locomotor activity, its acute administration-induced higher levels of locomotor activity in mice previously sensitized to ethanol than in controls which received saline. CONCLUSIONS: Our data suggest that besides the known psychological effects (fear of aversive effects) disulfiram efficacy on alcohol dependency treatment could also be due to its pharmacological interference in the brain neurotransmission.

Individual differences to repeated ethanol administration may predict locomotor response to other drugs, and vice versa.

Repeated administration of drugs may induce adaptations which affect the behavioral responses to the drug itself or to other drugs. Whether individual characteristics to repeated drug administration predict sensitivity to the effects of another drug is not clear. We evaluated whether or not mice that present higher vs. lower locomotor response after repeated treatment with ethanol display increased or decreased locomotor responses when challenged with methamphetamine or morphine, and vice versa. Mice received daily i.p. 2.2 g/kg ethanol (21 days), 1.0 mg/kg methamphetamine or 10 mg/kg morphine (10 days). According to the response presented during repeated drug treatment, mice were classified as HIGH or LOW activity groups. Locomotor activity was monitored after mice were challenged with saline, and 48 h later with a drug. Ethanol-treated mice were challenged with methamphetamine or morphine, methamphetamine- and morphine-treated animals were challenged with ethanol. After repeated treatment with ethanol or methamphetamine, locomotor sensitization was observed only in HIGH mice, not LOW mice. Ethanol-treated mice with HIGH activity showed sensitized, increased locomotor responses to methamphetamine (p<0.05), but not to morphine. Locomotor responses to ethanol were not affected by a previous history of methamphetamine treatment. Although repeated administration of morphine failed to induce sensitization, morphine-treated mice with HIGH activity presented sensitized locomotor responses after an ethanol challenge. The current experiments confirm important individual differences in response to repeated administration of ethanol, methamphetamine and morphine, which in some cases affected the locomotor response to a second drug challenge, in an asymmetrical pattern.

Does scopolamine block the development of ethanol-induced behavioral sensitization?

BACKGROUND: The cholinergic system is important in learning processes and probably influences behavioral sensitization to drugs. This study examined the effects of scopolamine (scop), a muscarinic antagonist, on the behavioral sensitization to ethanol (EtOH) stimulant effect in mice. METHODS: In experiments 1 and 2, male Swiss albino mice received saline or 1.0 mg/kg scop (s.c.) + saline or EtOH (i.p). (1.0 g/kg in experiment 1 and 2.2 g/kg in experiment 2), for 21 days. Locomotor activity (LA) was recorded once a week, being the treatment withdrawn for 7 days after the last test. On the 28th day (challenge 1), they were evaluated under saline or EtOH. In experiment 2, 3 days after the first challenge, they were tested in an open-field arena, under saline or 2.2 g/kg EtOH. Three days after this, mice were tested under saline or 1.0 mg/kg scop in the activity cages. RESULTS: Acutely, EtOH and scop did not alter the LA. However, when both drugs were coadministered, a significant reduction was observed. During the treatment, tolerance to the depressor effect was developed and behavioral sensitization observed only in the saline + 2.2 EtOH group. In challenge 1, the groups scop + 1.0 EtOH, saline + 2.2 EtOH, and scop + 2.2 EtOH presented higher levels of LA than that of the control groups. However, in challenge 2, conducted in a different setting, no differences between groups were observed. In challenge 3, when the animals received scop, both groups pretreated with 2.2 g/kg EtOH (saline + 2.2 EtOH and scop + 2.2 EtOH groups) presented higher levels of activity suggesting an interaction between EtOH and scop. CONCLUSIONS: Although the coadministration of scopolamine had impaired the observation of sensitization on the 21st day test, when the group scop + EtOH was challenged with scop + EtOH, it seems that the scop just masked the observation, but did not impair the development, of the EtOH-sensitization observed in the challenge with EtOH alone. The higher levels of LA in groups pretreated with EtOH only in the cages but not in the open-field arena confirm the importance of environmental factors, such as the context of drug administration and testing.

Effects of energy drink ingestion on alcohol intoxication.

BACKGROUND: Well-known reports suggest that the use of energy drinks might reduce the intensity of the depressant effects of alcohol. However, there is little scientific evidence to support this hypothesis. OBJECTIVE AND METHODS: The present study aimed at evaluating the effects of the simultaneous ingestion of an alcohol (vodka(37.5%v/v)) and an energy drink (Red Bull-3.57 mL/kg), compared with those presented after the ingestion of an alcohol or an energy drink alone. Twenty-six young healthy volunteers were randomly assigned to 2 groups that received 0.6 or 1.0 g/kg alcohol, respectively. They all completed 3 experimental sessions in random order, 7 days apart: alcohol alone, energy drink alone, or alcohol plus energy drink. We evaluated the volunteers' breath alcohol concentration, subjective sensations of intoxication, objective effects on their motor coordination, and visual reaction time. RESULTS: When compared with the ingestion of alcohol alone, the ingestion of alcohol plus energy drink significantly reduced subjects' perception of headache, weakness, dry mouth, and impairment of motor coordination. However, the ingestion of the energy drink did not significantly reduce the deficits caused by alcohol on objective motor coordination and visual reaction time. The ingestion of the energy drink did not alter the breath alcohol concentration in either group. CONCLUSIONS: Even though the subjective perceptions of some symptoms of alcohol intoxication were less intense after the combined ingestion of the alcohol plus energy drink, these effects were not detected in objective measures of motor coordination and visual reaction time, as well as on the breath alcohol concentration.