Encouraging greater empowerment for adolescents in consent procedures in social science research and policy projects.

The United Nations Convention on the Rights of the Child emphasizes the importance of allowing children and adolescents to influence decisions that are important to them following their age and maturity. This paper explores the principles, practices, and implications around using parental versus child/adolescent consent when participating in social science research and policy development. Experiences from two studies are presented: The Confronting Obesity: Co-creating policy with youth (CO-CREATE) and the Health Behaviour in School-aged Children (HBSC) study, a World Health Organization (WHO) Collaborative Cross-National study. Although parental consent may be an important gatekeeper for protecting children and adolescents from potentially harmful research participation, it may also be considered an obstacle to the empowerment of children and adolescents in case they want to share their views and experiences directly. This paper argues that evaluation of possible harm should be left to ethics committees and that, if no harm related to the research participation processes is identified and the project has a clear perspective on collaborating with the target group, adolescents from the age of 12 years should be granted the legal capacity to give consent to participate in the research project. Collaboration with adolescents in the development of the research project is encouraged.

Left behind: inequalities in the negative impacts of the COVID-19 pandemic among adolescents in the WHO European Region: impact of the COVID-19 pandemic on young people’s health and well-being from the findings of the HBSC survey round 2021/2022

This report summarizes findings from the Health Behaviour in School-aged Children survey round 2021/2022regarding the unequal impact of the COVID-19 pandemic on adolescents’ health and health behaviours in22 countries and regions of the WHO European Region. Risk factors contributed to different extents to thepandemic’s impact on adolescents’ health and health behaviours. More girls and 15-year-olds than boys andyounger adolescents reported negative impacts of the pandemic on the four health outcomes considered.The largest gender and age inequalities were seen in mental health. Social inequalities, such as havingan immigration background, coming from a family that was not well-off, having at least one unemployedparent and/or living in a single-parent household, were linked to adolescents experiencing negative impactsof the pandemic on their health and health behaviours in many countries and regions. Having experiencedthe hospitalization of a family member due to COVID-19 was also an important risk factor for negative healthand health behaviour outcomes in more than half of the countries and regions. The large cross-country/regionvariation in the contribution (or lack of contribution) of different risk factors to negative pandemic impactsunderlines the need for country-/region-specific interventions in times of crises.

Identifying Cardiovascular Risk Profiles Clusters among Mediterranean Adolescents across Seven Countries.

Cardiovascular diseases (CVDs) are the number one cause of death globally and are partially due to the inability to control modifiable lifestyle risk factors. The aim of this study was to analyze the profiles of adolescents from seven Mediterranean countries (Greece, Israel, Italy, Macedonia, Malta, Portugal, Spain) according to their modifiable lifestyle risk factors for CVD (overweight/obesity, physical activity, smoking, alcohol consumption). The sample consisted of 26,110 adolescents (52.3% girls) aged 11, 13, and 15 years who participated in the Health Behavior in School-aged Children (HBSC) survey in 2018 across the seven countries. Sociodemographic characteristics (sex, age, country of residence, socioeconomic status) and CVD modifiable lifestyle risk factors (overweight/obesity, physical activity, smoking, alcohol consumption) were recorded. A two-step cluster analysis, one-way analysis of variance, and chi-square test were performed. Four different cluster groups were identified: two low-risk groups (64.46%), with risk among those with low physical activity levels; moderate-risk group (14.83%), with two risk factors (unhealthy weight and low physical activity level); and a high-risk group (20.7%), which presented risk in all modifiable lifestyle risk factors. Older adolescents reported a higher likelihood of being in the high-risk group. Given that the adolescence period constitutes an important time for interventions aimed at CVD prevention, identifying profiles of moderate- and high-risk adolescents is crucial.

A Comparative Study of Health and Well-being Among Cisgender and Binary and Nonbinary Transgender Adolescents in Spain.

Purpose: The aim of this study was to describe the well-being and mental health of Spanish adolescents by gender identity using a nationally representative sample. Methods: The sample comprised 1212 15-18-year-old adolescents who participated in the 2018 Spanish edition of the international Health Behaviour in School-aged Children study. Of the total sample, 90 were identified as binary transgender adolescents, 213 as nonbinary transgender adolescents, and 909 as cisgender adolescents (selected through a matching process from an original sample of 17,375 cisgender adolescents). Comparisons of frequencies and means (chi-square, t-test, and analysis of variance) were used to analyze self-reported health, life satisfaction, health-related quality of life (HRQOL), psychosomatic complaints, and sense of coherence (SOC). Results: Nonbinary transgender adolescents reported the lowest levels of perceived excellent health (p < 0.001), the highest frequency of psychological complaints (p < 0.001) and physical complaints (p < 0.05), and a lower SOC (p < 0.05) compared with both cisgender and binary transgender adolescents. Likewise, nonbinary transgender adolescents reported lower levels of life satisfaction (p < 0.001) and HRQOL (p < 0.001) than cisgender adolescents. Conclusions: The differences found between binary and nonbinary transgender youth highlight the diversity within the transgender community. Both research and intervention programs should consider the unique experiences within the transgender community to adapt sensitively to their needs.

Cross-national time trends in adolescent alcohol use from 2002 to 2014.

BACKGROUND: Adolescent alcohol consumption is a major public health concern that should be continuously monitored. This study aims (i) to analyze country-level trends in weekly alcohol consumption, drunkenness and early initiation in alcohol consumption and drunkenness among 15-year-old adolescents from 39 countries and regions across Europe and North America between 2002 and 2014 and (ii) to examine the geographical patterns in adolescent alcohol-related behaviours. METHODS: The sample was composed of 250 161 adolescents aged 15 from 39 countries and regions from Europe and North America. Survey years were 2002, 2006, 2010 and 2014. The alcohol consumption and drunkenness items of the HBSC questionnaire were employed. Prevalence ratios and 95% confidence intervals were estimated using Poisson regression models with robust variance. RESULTS: Data show a general decrease in all four alcohol variables between 2002 and 2014 except for some countries. However, there is variability both within a country (depending on the alcohol-related behaviour under study) and across countries (in the beginning and shape of trends). Some countries have not reduced or even increased their levels in some variables. Although some particularities have persisted over time, there are no robust patterns by regions. CONCLUSIONS: Despite an overall decrease in adolescent alcohol consumption, special attention should be paid to those countries where declines are not present, or despite decreasing, rates are still high. Further research is needed to clarify factors associated with adolescent drinking, to better understand country specificities and to implement effective policies.

Mental Health in Adolescents with a Migration Background in 29 European Countries: The Buffering Role of Social Capital.

Previous research is inconclusive as to whether having an immigration background acts as a risk factor for poor mental health in adolescents, and furthermore, what contribution the social context in which adolescents grow up may make. To address these questions, the current study uses an integrative resilience framework to investigate the association between immigration background and adolescent mental health, and the moderating role of social capital at the individual, the school, and the national level. The study uses data gathered from nationally representative samples of adolescents aged 11, 13, and 15 years (Ngirls = 63,425 (52.1%); Mage = 13.57, SD = 1.64) from 29 countries participating in the 2017/18 Health Behaviour in School-aged Children (HBSC) study. Data analysis reveals that first- and second-generation immigrants reported higher levels of life dissatisfaction and psychosomatic symptoms than their native peers, and that this association varied across schools and countries. In addition, social capital was found to moderate the association between immigration background and adolescent mental health. Individual-level social support from peers and family and national-level trust protected against poor mental health in adolescents with an immigration background, while the opposite was true for individual-level teacher support. Supportive teacher-student relationships were found to provide more protection against poor mental health for native adolescents than for immigrant adolescents. Our findings indicate the importance of taking an ecological approach to design interventions to reduce the negative effects of having an immigration background on adolescent mental health.

Intersectionality and Adolescent Mental Well-being: A Cross-Nationally Comparative Analysis of the Interplay Between Immigration Background, Socioeconomic Status and Gender.

PURPOSE: Intersectionality theory highlights the importance of the interplay of multiple social group memberships in shaping individual mental well-being. This article investigates elements of adolescent mental well-being (life dissatisfaction and psychosomatic complaints) from an intersectional perspective. It tests mental well-being consequences of membership in combinations of multiple social groups and examines to what extent such intersectional effects depend on the national context (immigration and integration policies, national-level income, and gender equality). METHODS: Using Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy, we assessed the role of the national context in shaping the interplay between immigration background, socioeconomic status, and gender, using data from 33 countries from the 2017/2018 Health Behaviour in School-aged Children survey. RESULTS: We found no uniform intersectionality effects across all countries. However, when allowing the interplay to vary by national context, results did point toward some intersectional effects. Some aggravated negative effects were found for members of multiple disadvantaged social groups in countries with low levels of income equality and restrictive migration policies, whereas enhanced positive effects were found for members of multiple advantaged groups in these countries. Similarly, mitigated negative effects of membership in multiple disadvantaged groups were shown in countries with higher levels of income equality and more inclusive migration policies, whereas mitigated positive effects were found for multiply advantaged individuals. Although for national-level gender equality results pointed in a similar direction, girls' scores were counterintuitive. High national-level gender equality disproportionately benefitted groups of disadvantaged boys, whereas advantaged girls were doing worse than expected, and reversed effects were found for countries with low gender equality. CONCLUSIONS: To fully understand social inequalities in adolescent mental well-being, the interplay between individual-level and national-level indicators must be explored.

The Role of Body Image in Internalizing Mental Health Problems in Spanish Adolescents: An Analysis According to Sex, Age, and Socioeconomic Status.

During adolescence there is a relatively high prevalence of weight problems and eating disorders. Furthermore, body image plays an important role in weight control and eating behaviors as well as in mental health. This study analyses the influence of body mass index, perception of being overweight, and body image satisfaction (BIS) on internalizing symptoms related to mental health in adolescents. In addition, sex, age, socioeconomic status (SES), dieting, and physical activity are taken into consideration. This research is based on the international study Health Behaviour in School-aged Children (HBSC). The sample consists of 4531 Spanish adolescents from 13 to 18 years old. Participants were selected through random multi-stage sampling stratified by conglomerates. Two instruments were employed: the HBSC questionnaire and the Youth Self-Report (Achenbach System of Empirically Based Assessment, ASEBA). Results demonstrated that BIS -the emotional component related to body image- was the main predictor of adolescent internalizing symptoms. In addition, results show double-inequalities according to the interaction effects of sex, age, and SES. Likewise, interesting results are shown regarding how dieting behaviors to lose or gain weight/volume and physical activity relate to body image perception and satisfaction, as well as with internalizing symptoms. This study highlights important body image aspects relevant to intervention and prevention of internalized mental health problems in adolescence.

Direct and Indirect Influences of Objective Socioeconomic Position on Adolescent Health: The Mediating Roles of Subjective Socioeconomic Status and Lifestyles.

The use of composite indices and subjective measures to evaluate socioeconomic position, taking into account the effect of inequalities on adolescent health-related behaviors, can contribute to understanding the effect of inequalities on health during adolescence. The aim of this study was to examine the direct and indirect contribution of objective and subjective socioeconomic factors in a broad range of health and lifestyles outcomes. The data come from a representative sample of adolescents (N = 15,340; M age = 13.69) of the Health BehaviorinSchool-agedChildren study in Spain. Structural equation modeling was used for data analysis. A global index for evaluating objective socioeconomic position predicted both health and healthy lifestyles. Subjective socioeconomic status mediated the relationship between objective socioeconomic position and health but did not have a significant effect on healthy lifestyles when objective indicators were considered. Lastly, fit indices of the multiple-mediator model-including the direct effect of objective socioeconomic position on health and its indirect effects through the subjective perception of wealth and lifestyles-explained 28.7% of global health variance. Interventions aimed at reducing the impact of health inequalities should address, in addition to material deprivation, the psychological and behavioral consequences of feeling poor.

Subtle metabolic alterations in adolescents with obesity and polycystic ovarian syndrome. / Alteraciones metabólicas sutiles en adolescentes con obesidad y síndrome de ovario poliquístico.

Objective: To evaluate the frequency of some subtle metabolic alterations in a group of adolescents with obesity and polycystic ovary syndrome (PCOS). Materials and Methods: A cross-sectional, comparative study was conducted in a group of adolescents with obesity, and characterized as with or without PCOS according with the Rotterdam Consensus. Medical history, anthropometry, gynecologic pelvic ultrasound (to evaluate ovarian volumes, number of antral follicles and endometrial width), as well as serum glucose, insulin, lipoproteins, interleukin-6, tumor necrosis factor alpha, total testosterone, dehydroepiandrosterone, sexual hormones binding globulin, leptin, adiponectin and insulin-like growth factor 1, the free-androgen index, free and available testosterone, and homeostatic model assessment index were calculated. For statistics, mean and standard deviation, or median and ranges were used for description as appropriate. Likewise, Student t-test or Mann-Whitney test were used for comparisons. Results: From a sample of 180 adolescents, 47 attached to selection criteria. Mean age was 13.5 year and Z-score 2.5. Eighty percent of adolescents presented central distribution of body fat and 95% hyperinsulinemia. The more frequent dyslipidemias were hypertriglyceridemia in 57% and hypercholesterolemia in 12.8%; 25.5% of adolescents presented two out of three criteria for polycystic ovary syndrome (PCOS). Body mass index and insulin were correlated with free testosterone, but the multivariate analysis demonstrated that the magnitude of the association was significantly higher in SOP patients. Conclusions: The metabolic alterations detected in obese adolescents with SOP suggest that the clinical manifestations that accompany the syndrome characterize the PCOS as a metabolic disease, which carry important health risks at short, medium and long term. Therefore, they merit intervening actions to prevent, diagnose and provide timing treatment in order to limit the damage in the course of the natural history of PCOS.

Indicadores para detectar y evaluar el impacto de las desigualdades socioeconómicas en los estilos de vida y la salud de los adolescentes españoles / No disponible

En este estudio se comparan distintos indicadores socioeconómicos en cuanto a su capacidad para predecir desigualdades en la salud y los estilos de vida de la población adolescente. Los resultados muestran que la relación entre los diferentes indicadores socioeconómicos, a pesar de ser significativa, es débil, sugiriendo que cada uno evalúa en cierto grado aspectos distintos del constructo socioeconómico. Además, mientras que el nivel educativo de los progenitores, y especialmente el nivel educativo de las madres, es la variable que muestra mayor capacidad para detectar desigualdades en los estilos de vida adolescentes, la percepción subjetiva de riqueza se revela como el predictor más importante de las desigualdades en salud. Adicionalmente, los resultados de este estudio muestran que no todas las conductas relacionadas con los estilos de vida adolescente y su bienestar están igualmente influenciadas por determinantes socioeconómicos. De esta forma, mientras que las conductas relacionadas con los hábitos de alimentación o la salud adolescente se ven fuertemente influidas por factores socioeconómicos, el efecto de las desigualdades es menos claro en conductas tales como el consumo de tabaco y alcohol. Esta investigación subraya la importancia de la elección de un determinado indicador en estudios que evalúan los efectos de las desigualdades socioeconómicas en los estilos de vida y la salud adolescente

In this research we compare different socioeconomic indicators according to their capacity to detect socioeconomic inequalities in adolescent health and lifestyles. The results showed that the relationship between the different socioeconomic indicators, despite being significant, had a weak association, suggesting that each indicator evaluates different dimensions of the socioeconomic construct. In addition, whereas parental education, and especially maternal education, was the most relevant indicator for predicting socioeconomic inequalities in adolescent lifestyles, the perceived family wealth was the most important predictor of inequalities in adolescent health. Additionally, the results of this study show that not all behaviours related to healthy lifestyles and adolescent health were equally influenced by socioeconomic determinants. Along these lines, whereas eating behaviours or health outcomes showed to be highly influenced by socioeconomic factors, the impact of socioeconomic inequalities in behaviours such as alcohol consumption or tobacco use was less clear. This research highlights the importance of choosing a specific indicator in studies that evaluate the effects of socioeconomic inequalities in adolescent health and lifestyles

TLR4 elimination prevents synaptic and myelin alterations and long-term cognitive dysfunctions in adolescent mice with intermittent ethanol treatment.

The adolescent brain undergoes important dynamic and plastic cell changes, including overproduction of axons and synapses, followed by rapid pruning along with ongoing axon myelination. These developmental changes make the adolescent brain particularly vulnerable to neurotoxic and behavioral effects of alcohol. Although the mechanisms of these effects are largely unknown, we demonstrated that ethanol by activating innate immune receptors toll-like receptor 4 (TLR4), induces neuroinflammation and brain damage in adult mice. The present study aims to evaluate whether intermittent ethanol treatment in adolescence promotes TLR4-dependent pro-inflammatory processes, leading to myelin and synaptic dysfunctions, and long-term cognitive impairments. Using wild-type (WT) and TLR4-deficient (TLR4-KO) adolescent mice treated intermittently with ethanol (3.0g/kg) for 2weeks, we show that binge-like ethanol treatment activates TLR4 signaling pathways (MAPK, NFκB) leading to the up-regulation of cytokines and pro-inflammatory mediators (COX-2, iNOS, HMGB1), impairing synaptic and myelin protein levels and causing ultrastructural alterations. These changes were associated with long-lasting cognitive dysfunctions in young adult mice, as demonstrated with the object recognition, passive avoidance and olfactory behavior tests. Notably, elimination of TLR4 receptors prevented neuroinflammation along with synaptic and myelin derangements, as well as long-term cognitive alterations. These results support the role of the neuroimmune response and TLR4 signaling in the neurotoxic and behavioral effects of ethanol in adolescence.

Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice.

Exposure to social defeat stress increases the rewarding effects of psychostimulants in animal models, but its effect on 3,4-methylenedioxymethylamphetamine (MDMA) reward has received little attention. In the present study, we evaluated the influence of social defeat on the rewarding effects of MDMA in adolescent [postnatal day (PND) 29-40] and adult (PND 50-61) male mice using the conditioned place preference paradigm. Experimental mice were exposed to social defeat in an agonistic encounter before each session of conditioning with 1.25 or 10 mg/kg of MDMA. The effects of social defeat on corticosterone levels and the motor or the anxiogenic effects of MDMA were also evaluated. Mice exposed to social defeat during adulthood did not show conditioned place preference after conditioning with either dose of MDMA. Conversely, social defeat did not affect the anxiogenic and motor effects of MDMA. Adult mice exposed to social defeat showed higher levels of corticosterone than their controls and adolescent mice. Social stress did not induce behavioural effects in adolescent mice. Our results show that stress induced by social defeat decreases the sensitivity of adult mice to the rewarding effects of MDMA.

The novelty-seeking phenotype modulates the long-lasting effects of intermittent ethanol administration during adolescence.

The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg) on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels--measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg) was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype.

Intermittent ethanol exposure increases long-lasting behavioral and neurochemical effects of MDMA in adolescent mice.

RATIONALE: Heavy binge drinking is increasingly frequent among adolescents, while ethanol (EtOH) is often used in combination with 3,4-methylenedioxymethamphetamine (MDMA). OBJECTIVES: The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on motor activity, anxiety, and social behavior were evaluated in adult mice. The concentration of brain monoamines in the striatum, cortex, and hippocampus was measured following the behavioral test. METHODS: Adolescent OF1 mice were exposed to ethanol (1.25 g/kg) on two consecutive days at 48-h intervals over a 14-day period (from PND 29 to 42). A total of eight injections of MDMA (10 or 20 mg/kg) were administered twice daily at 4-h intervals over two consecutive days, and this schedule was repeated 6 days later (PND 33, 34, 41, and 42). Behavioral tests and analysis of brain monoamines took place on PND 64 to 67. RESULTS: Exposure to MDMA during adolescence increased the anxiogenic response in the elevated plus maze, with adult mice spending less time in the open arms of the maze and exhibiting lower concentrations of DA in the striatum. A pattern of ethanol administration modeling binge drinking during adolescence enhanced these effects and undermined the hyperthermic response induced by MDMA. Passive avoidance was affected only when EtOH was administered alone. CONCLUSIONS: Juvenile administration of MDMA and alcohol was found to cause a decrease in monoamine levels in adulthood, as well as changes in social interaction behaviors, locomotor activity, increase measures of anxiety in the elevated plus maze (EPM), and decrease step-through latencies in passive avoidance test.

Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice.

BACKGROUND: Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice. METHODS: In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN. RESULTS: A low dose of WIN 55212-2 (0.1 mg/kg) increased the rewarding effects of low doses of MDMA (1.25 mg/kg), although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg) was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg). The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA-induced CPP. CONCLUSIONS: These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.

Gestational exposure to cocaine alters cocaine reward.

Exposure of the developing foetus to drugs of abuse during pregnancy may lead to persistent abnormalities of brain systems involved in drug addiction. Mice prenatally exposed to cocaine (25 mg/kg), physiological saline or non-treated during the last 7 days of pregnancy were evaluated in adulthood for the rewarding properties of cocaine (3, 25 and 50 mg/kg), using the conditioned place preference procedure. Dams treated with physiological saline gained significantly less weight over the course of gestation than controls; no other differences were observed in the maternal and offspring data. All the animals developed preference to 3 and 25 mg/kg of cocaine, but those treated prenatally with cocaine did not develop preference after receiving the highest cocaine dose. In these mice, the motor activity in response to 50 mg/kg showed a small decrease. Although a reduced response to the highest cocaine dose can be argued, we suggest that the lack of preference obtained is more likely attributable to an increased sensitivity to the environmental cues associated during training to an aversive effect of this cocaine dose. The aversive properties of cocaine seem to be more apparent and to prevail over the rewarding action of the highest dose in exposed animals. These findings indicate that recurrent gestational cocaine exposure results in permanent (mal)adaptations of the structure and function of brain reward systems.

Prenatal cocaine alters later responses to morphine in adult male mice.

Mice prenatally exposed to cocaine (25 mg/kg), physiological saline or non-treated during the last 6 days of pregnancy were evaluated as adults for the rewarding properties of 2 mg/kg of morphine, using the conditioned place preference (CPP) procedure. Likewise, isolated animals underwent a social interaction test with conspecifics after receiving the same morphine dose. Unlike control or animals pre-treated with saline, subjects prenatally treated with cocaine did not develop CPP with this dose of morphine. Only cocaine-exposed animals showed increased threat, avoidance and fleeing during the social encounter. No differences in motor effects of morphine were observed. Analysis of monoamines revealed effects of housing conditions, isolated animals having fewer DOPAC but higher levels of HVA than those grouped, but in both groups there was a decrease in DOPAC in cocaine- and saline-treated mice. Prenatal cocaine exposure decreases the response to the rewarding properties of drugs in mature offspring. They also implicate cocaine consumption during pregnancy could affect the response of offspring to take other drugs of abuse.

Gamma-hydroxybutyric acid affects the acquisition and reinstatement of cocaine-induced conditioned place preference in mice.

Cocaine addicts very often use different combinations of cocaine and other drugs of abuse such as gamma-hydroxybutyric acid. The objective of the present work was to evaluate the impact of gamma-hydroxybutyric acid administration on the rewarding actions of cocaine, using the conditioned place preference procedure. Cocaine-induced conditioned place preference (50 mg/kg) was studied after pairing this drug with different gamma-hydroxybutyric acid doses (6.25, 12.5, 25, 50 and 100 mg/kg) during either the acquisition or the expression phase of the procedure. After conditioned place preference had been established, and the preference was extinguished, a reinstatement was induced by a dose of cocaine half of that used to produce conditioning, or by gamma-hydroxybutyric acid alone or by both drugs together. The doses of 12.5 and 100 mg/kg of gamma-hydroxybutyric acid blocked the acquisition of cocaine-induced conditioned place preference, and no dose affected the expression of this conditioning. Reinstatement was abolished only with the dose of 25 mg/kg gamma-hydroxybutyric acid, which did not reinstate the preference by itself. This is the first study evaluating the effects of gamma-hydroxybutyric acid on the rewarding properties of cocaine using the conditioned place preference procedure. The principal conclusion of the study is that gamma-hydroxybutyric acid does not enhance the rewarding effect of cocaine, and within a narrow margin of effective doses, blocks the acquisition and reinstatement of cocaine-induced preference.

GHB ameliorates naloxone-induced conditioned place aversion and physical aspects of morphine withdrawal in mice.

RATIONALE: Gamma-hydroxybutyric acid (GHB) is a naturally occurring substance in the brain, the administration of which has proved useful in the treatment of the opiate withdrawal symptoms in humans. OBJECTIVES: The aim of the present work was to validate this beneficial effect on the physical and motivational aspects of morphine withdrawal in mice. METHODS: In a first experiment, animals rendered morphine-dependent were conditioned to develop a place aversion (CPA) to the compartment paired with naloxone administration in a two-chamber apparatus. The conditioning phase consisted of three pairings of either naloxone (0.250 mg/kg) or vehicle in one compartment, both with similar time allotments during the preconditioning test. During the testing phase, mice were again allowed to explore the entire apparatus. GHB (6, 12.5, 25, and 50 mg/kg) was administered during either the acquisition or expression phase of this conditioning. In a second experiment, the capacity of GHB to ameliorate the intensity of physical signs of morphine withdrawal was evaluated. RESULTS: GHB blocked CPA in both phases: administered during acquisition (from 12.5 mg/kg and higher) as well as in the expression phase (from 6 mg/kg, except for 25 mg/kg). It also decreased the intensity of physical signs of morphine withdrawal to near control levels measured by the modified Gellert-Holtzman scale (25 mg/kg and higher). Decreases in jumping, body shakes, and paw tremor were also observed. CONCLUSIONS: Our results support the idea that GHB ameliorates both aspects of morphine withdrawal, physical as well as motivational signs.