C57BL/6J offspring mice reared by a single-mother exhibit, compared to mice reared in a biparental parenting structure, distinct neural activation patterns and heightened ethanol-induced anxiolysis.

RATIONALE: Parenting experiences with caregivers play a key role in neurodevelopment. We recently reported that adolescents reared by a single-mother (SM) display an anxiety-prone phenotype and drink more alcohol, compared to peers derived from a biparental (BP) rearing condition. OBJECTIVES: To investigate if SM and BP offspring infant mice exhibit differential sensitivity to ethanol-induced locomotor activity and differential activity patterns in brain areas related to anxiety response. We also analyzed anxiety response and ethanol-induced anxiolysis in SM and BP adolescents. METHODS: Mice reared in SM or BP conditions were assessed for (a) ethanol-induced locomotor activity at infancy, (b) central expression of Fos-like proteins (likely represented mostly by FosB, a transcription factor that accumulates after chronic stimuli exposure and serves as a molecular marker of neural plasticity) and cathecolaminergic activity, and (c) anxiety-like behavior and ethanol-induced anxiolysis in adolescence. RESULTS: Infant mice were sensitive to the stimulating effects of 2.0 g/kg alcohol, regardless parenting structure. SM mice exhibited, relative to BP mice, a significantly greater number of Fos-like positive cells in the central amygdala and basolateral amygdala nuclei. Ethanol treatment, but not parenting condition, induced greater activation of dopaminergic neurons in ventral tegmental area. SM, but not BP, adolescent mice were sensitive to ethanol-induced anxiolysis. CONCLUSIONS: These results highlight the complex relationship between parenting experiences and neurodevelopment. The SM parenting may result in greater neural activation patterns in brain areas associated with anxiety response, potentially contributing to increased basal anxiety and alcohol sensitivity.

Cognitive Distortions Associated with Alcohol and Marijuana Use in Uruguayan Citizens.

Background: Psychological distress (i.e., incipient symptoms of anxiety, stress, and depression) may promote substance use through increased emission of cognitive distortions. These are automatic irrational thoughts that can promote distress, which in turn increases substance use. Aim: This study analyzed, in a sample of Uruguayan citizens, the unique contribution of cognitive distortions on the frequency and quantity of alcohol or marijuana use, over and above the contribution of psychological distress or the use of emotion regulation strategies. We also assessed whether these variables were associated with having initiated or resumed the use of a substance. Methods: A survey asked about alcohol and marijuana use, psychological distress, emotion regulation strategies, and cognitive distortions. The study comprised a convenience sample of 1132 participants (Mean age = 29.07 ± 8.19 years, 72.26% women). Separate hierarchical linear regression analyses were conducted on the frequency and quantity of alcohol or marijuana use, whereas a logistic regression was applied on having initiated or resumed the use of a substance. Results: Several cognitive distortions were significant predictors of frequency and quantity of alcohol consumption or frequency of marijuana use, over and above psychological distress. Differential emission of automatic thoughts was also associated, along with higher scores of psychological distress, with a significantly higher probability of having initiated the use of a new substance or having resumed the use of a substance. Conclusions: Cognitive distortions may promote alcohol and marijuana use. Interventions aimed at modifying these distortions should be considered to reduce the emission of these behaviors.

IMPULSIVITY, mental health STATE and emotion regulation MODULATE alcohol and marijuana use in a sample of Argentinean citizens.

Impulsivity and substance-related outcomes share a complex relationship, as various facets of impulsivity exhibit distinct associations with different drug-related outcomes. This study examines the associations between frequency and quantity of alcohol and marijuana use, with impulsivity traits, psychological distress, and the utilization of emotion regulation strategies. A survey asked Argentinian citizens (n=1507, 356 men) about frequency and quantity of alcohol or marijuana use on each day of a typical week, as well as anxiety, stress and depression symptoms (DASS-21), impulsivity-like traits (UPPS-P) and emotion regulation strategies (ERQ). The two-month prevalence of alcohol or marijuana use was 80.1%, and 27.2%, respectively. Lower premeditation was significantly (p<.05) and negatively associated with both frequency and quantity of alcohol consumed, whereas negative and positive urgency were positively and significantly (p<.05) associated with quantity of alcohol or marijuana use, respectively. Greater depression symptoms predicted greater quantity of alcohol use; whereas lower emotional suppression or lower cognitive reappraisal were significantly (p<.05) associated with a greater frequency of alcohol or marihuana use. Sensation seeking was significantly (p<.05) and positively associated with frequency of marijuana use. Individuals with higher levels of impulsivity-like traits, higher levels of depression or lower use of emotional regulation abilities appeared to be at a higher risk of alcohol or marijuana use. In this sample, the use of alcohol (though not marijuana) seems to fit a negative reinforcement pathway. The study suggests that individuals with risk factors for drug misuse could benefit from interventions aimed at enhancing emotion regulation.

Neurobehavioral alterations induced by third-trimester gestation-equivalent ethanol exposure are inhibited by folate administration.

Prenatal ethanol exposure (PEE) causes several neurobehavioral impairments in the fetus. Postnatal days (PDs) 4-9 in rodents are considered equivalent to the third trimester of gestation in humans. This period is characterized by high rates of synaptogenesis and myelination and the maturation of key structures and transmitter systems. Nutritional supplements, such as folate, have gained attention as putative treatments to mitigate detrimental effects of PEE. Folate is crucial for DNA synthesis and amino acid metabolism and heightens antioxidant defenses. The present study examined neurobehavioral effects of the concurrent administration of folate (20 mg/kg/day) and ethanol (5 g/kg/day) during PDs 4-9 in male and female Wistar rats. During PDs 16-18, the rat pups were tested for anxiety-like and exploratory activity in the light-dark box (LDB), open field (OF), and concentric square field (CSF) tests. After weaning, they were tested for sucrose preference and ethanol intake. Neonatal ethanol exposure reduced body weight in infancy but did not enhance ethanol self-administration or significantly affect performance in the OF or LDB. Neonatal ethanol exposure also reduced sucrose intake in the preference test and increased shelter-seeking in the CSF, and folate significantly inhibited these effects. The present findings suggest that folate, a treatment that is devoid of serious side effects, can ameliorate some neurobehavioral effects of PEE.

Juvenile variable stress modulates, in female but not in male Wistar rats, ethanol intake in adulthood.

Early stress can increase vulnerability to psychopathological disorders, including substance use disorders. The effects of stress in the juvenile period of the rat, that extends between weaning and the onset of adolescence (equivalent to late human childhood), have received little attention. This study assessed short and long-term behavioral effects of juvenile stress, with a focus on effects on ethanol intake. Male and female Wistar rats were exposed to variable stress (restraint, elevated platform, forced swimming, and social instability) or to restraint stress only, between postnatal days 26 to 29 (PDs 26-29). During adolescence, patterns of anxiety (PD 31) and depression (PD 33), ethanol intake (PDs 36-45) and behavioral sensitivity to the effects of acute stress (PD 47) were evaluated. In adulthood, alcohol ingestion was assessed through two-bottle ethanol intake tests (PDs 75-85). An additional experiment measured blood ethanol levels after a limited access intake session in adolescence. Exposure to juvenile variable stress exerted very mild effects in adolescence, but reduced ethanol ingestion in adulthood, in females only. Ethanol intake during the limited access session was significantly correlated to blood alcohol levels. The results indicate that a schedule of juvenile variable stress that did not significantly alter anxiety-related behaviors induced, nonetheless, sexually dimorphic effects on ethanol intake in adulthood. Early stress exposure that reduced alcohol intake in Wistar rats has been associated with changes on brain opioid and dopamine receptors. These results highlight the impact of early stress exposure on adult female ethanol consumption and its possible underlying neurobiological changes, involving opioid and dopamine receptors.

Malestar psicológico y su relación con edad, sexo, trabajo, estudio, zona de residencia, en jóvenes uruguayos / Association between Psychological Discomfort and Age, Sex, Work, Study, Zone of Residence in Uruguayan Young People / Associação entre sofrimento psicológico e idade, sexo, trabalho, estudo e área de residência, em jovens uruguaios

El malestar psicológico está asociado a una mayor probabilidad de desarrollar cuadros psicopatológicos de alta incidencia en Uruguay, como los trastornos por uso de sustancias o el suicidio. Es importante, por lo tanto, analizar determinantes de dicho malestar. Este trabajo analiza, mediante una encuesta aplicada a 1527 uruguayos de entre 18 a 30 años, variables asociadas al malestar psicológico. Fue aplicada la escala de malestar psicológico de Kessler (2002), determinándose el sexo y la edad como predictores significativos, bivariados y multivariados, de los niveles de malestar. El tamaño de estos efectos fue, sin embargo, pequeño. Las mujeres y las personas jóvenes expresan mayores niveles de malestar que los hombres y las personas mayores, respectivamente. El malestar psicológico no estuvo significativamente asociado a la cantidad de horas dedicadas a trabajo o estudio, al nivel educativo ni a la región del país en que se reside. Este trabajo provee conocimiento sobre los niveles normales ­de referencia­ de malestar psicológico en jóvenes uruguayos, y factores asociados a estos niveles

In Uruguay, psychological distress is associated with a higher probability of developing highly prevalent psychopathological conditions such as addictions or suicide. It is important, therefore, to analyze factors associated with such distress. This work analyzes, via a survey applied to 1527 Uruguayans between 18 and 30 years old, variables associated with psychological distress. We applied the Kessler psychological distress scale and determined that sex and age were significant predictors, at the bivariate and multivariate level, of psychological distress. The size of these effects was, however, small. Women and youngsters express higher levels of distress than men and older people, respectively. Psychological distress was not significantly associated with the number of hours dedicated to work or study; educational level; or the region of the country in which one resides. This work provides knowledge about the normal -reference- levels of psychological distress in young Uruguayans and factors associated with these levels, which can result in a powerful and useful tool for planning mental health policies for this population.

O sofrimento psicológico está associado a uma maior probabilidade de desenvolver condições psicopatológicas de alta incidência no Uruguai, como transtornos por uso de substâncias ou suicídio. É importante, por tanto, analisar os determinantes desse sofrimento. Este trabalho analisa, por meio de uma pesquisa aplicada a 1527 uruguaios entre 18 e 30 anos, variáveis associadas ao sofrimento psicológico. Aplicou-se a escala de so-frimento psicológico de Kessler (2002), determinando sexo e idade como preditores bivariados e multivariados significativos dos níveis de sofrimento. A dimensão destes efeitos foi, no entanto, pequena. As mulheres e os jovens expressam níveis mais elevados de sofrimento do que os homens e os idosos, respectivamente. O sofrimento psicológico não foi significativamente associado ao número de horas dedicadas ao trabalho ou estudo, ao nível de escolaridade ou à região do país em que se reside. Este trabalho proporciona conhecimento sobre os níveis normais - de referência - de sofrimento psicológico em jovens uruguaios e os fatores associados a esses níveis

Binging from Food to Alcohol: A Sequential Interaction Between Binging Behaviors in Male Wistar Rats.

The development of excessive alcohol (ethanol) and/or highly palatable food self-administration is an essential task to elucidate the neurobiological mechanisms that underlie these behaviors. Previous work has highlighted that ethanol self-administration is modulated by both the induction of aversive states (i.e., stress or frustration) and by the concurrent availability of appetitive stimuli (e.g., food). In our protocol, rats are food deprived for three days until they reach 82%-85% of their ad libitum weight. After that, rats are exposed daily for 10 days to a brief binge or control eating experience with highly sugary and palatable food (i.e., the ingestion of 11.66 and 0.97 kcal/3 min, respectively), which is followed by a two-bottle-choice test (ethanol vs. water) in their home cages for 90 min. This model induces robust binge eating, which is followed by a selective increase in ethanol self-administration. Therefore, this protocol allows to study: a) behavioral and neurobiological factors related to binge eating, b) different stages of alcohol use, and c) interactions between the latter and other addictive-like behaviors, like binge eating.

A review on the reciprocal interactions between neuroinflammatory processes and substance use and misuse, with a focus on alcohol misuse.

Background: The last decade has witnessed a surge of findings implicating neuroinflammatory processes as pivotal players in substance use disorders. The directionality of effects began with the expectation that the neuroinflammation associated with prolonged substance misuse contributes to long-term neuropathological consequences. As the literature grew, however, it became evident that the interactions between neuroinflammatory processes and alcohol and drug intake were reciprocal and part of a pernicious cycle in which disease-relevant signaling pathways contributed to an escalation of drug intake, provoking further inflammation-signaling and thereby exacerbating the neuropathological effects of drug misuse.Objectives: The goal of this review and its associated special issue is to provide an overview of the emergent findings relevant to understanding these reciprocal interactions. The review highlights the importance of preclinical and clinical studies in testing and validation of immunotherapeutics as viable targets for curtailing substance use and misuse, with a focus on alcohol misuse.Methods: A narrative review of the literature on drug and neuroinflammation was conducted, as well as articles published in this Special Issue on Alcohol- and Drug-induced Neuroinflammation: Insights from Pre-clinical Models and Clinical Research.Results: We argue that (a) demographic variables and genetic background contribute unique sensitivity to drug-related neuroinflammation; (b) co-morbidities between substance use disorders and affect dysfunction may share common inflammation-related signatures that predict the efficacy of immunotherapeutic drugs; and (c) examination of polydrug interactions with neuroinflammation is a critical area where greater research emphasis is needed.Conclusions: This review provides an accessible and example-driven review of the relationship between drug misuse, neuroinflammatory processes, and their resultant neuropathological outcomes.

Folate administration ameliorates neurobehavioral effects of prenatal ethanol exposure.

Background: Prenatal ethanol exposure (PEE) induces heightened ethanol intake at adolescence in preclinical studies. Ethanol intake alters the absorption of folate, a methyl-group donor critical for numerous cellular functions. The prenatal administration of folate is, therefore, a promising approach to reduce the effects of PEE.Objectives: Experiment 1 determined if prenatal folate modulated the effects of PEE on ethanol intake, anxiety-like response, and exploratory behaviors (Experiment 1) in Wistar rats. Experiment 2 assessed, in rats not given PEE, if postnatal folate reversed effects of ethanol exposure at postnatal days 28-42. Experiment 3 assessed if folate altered blood ethanol levels (BELs).Methods: Experiment 1 involved 242 (125 male) adolescent Wistar rats derived from dams given folate (20 mg/kg, gestational days - GD- 13-20) + ethanol (2.0 g/kg, GD 17-20), ethanol, or vehicle only at pregnancy. Experiment 2 involved 29 male adolescents administered vehicle or ethanol doses co-administered or not with folate. In Experiment 3 twelve adult females were tested for BELs after folate administration. These tests were applied: intake tests, light dark box (LDB), elevated plus maze, open field and concentric square field.Results: PEE heightened ethanol intake (η2 ps = 0.06-07) and induced hyperactivity and a reduced latency to exit the white area of the LDB (η2 ps = 0.12-17). These effects were partially inhibited by folate (p > .05). Rats exposed to ethanol exposure at adolescence exhibited reduced motor activity (η2 p = .17), regardless of folate treatment. Folate did not affect BELs.Conclusion: Folate administration should be considered as a preventive or acute treatment to attenuate the neurobehavioral effects of PEE.

Binge eating promotes ethanol self-administration in female rats with a history of intermittent ethanol exposure at adolescence.

BACKGROUND: Ethanol drinking begins during adolescence and, particularly when occurs in a binge-like pattern, exerts lingering adverse consequences. Pre-clinical studies indicate that intermittent ethanol exposure (IEA, a model of repeated ethanol intoxication), or binge eating (BE) can increase subsequent ethanol consumption. It is unknown if the promoting effects of BE upon ethanol drinking are found in female rats and are modulated by IEA at adolescence. This study assessed interactive effects between IEA and BE, upon ethanol drinking. METHODS: Female Wistar rats were given 4.0 g/kg ethanol, every other day from postnatal day 25-45. At adulthood, they were exposed to sessions in which a brief offering of a sizeable portion of highly palatable sugary pills was followed by a 120-min exposure to an ethanol bottle. RESULTS: Exploratory activity and recognition memory was not affected by the IEA. Glutathione peroxidase and catalase activity, and lipid peroxidation (measured in blood and brain at the end of the procedure) were not significantly affected by IEA or BE exposure. BE alone had a mild promoting effect on ethanol ingestion. Those rats that underwent IEA and BE, however, exhibited heightened and sustained ethanol self-administration (average of 2.12 g/kg/120 min, vs 1.15 g/kg/120 min of the other groups), that persisted throughout the BE sessions. IEA and a history of BE also promoted ethanol intake or preference in a two-bottle endpoint test. CONCLUSION: The study suggests that exposure to IEA exerts, when followed by BE at adulthood, promoting effects upon ethanol intake, particularly at concentrations ≥ 6%.

Percepción de riesgo asociada al consumo de alcohol, tabaco y marihuana en estudiantes universitarios: diferencias en función del consumo y del sexo / Perceived risk associated with the consumption of alcohol, tobacco and marijuana: differences according to use and gender

Resumen El consumo de alcohol, tabaco y marihuana presenta una alta prevalencia entre adultos emergentes universitarios. Una variable que incide en el consumo de estas tres sustancias psicoactivas es la percepción de riesgo asociada a dicha conducta. Este estudio examinó -en adultos emergentes universitarios argentinos- la relación bi o multivariada, entre el riesgo percibido de consumir alcohol, tabaco y marihuana, y el consumo propiamente dicho de estas sustancias. Se analizaron también variaciones en la percepción de riesgo en función del sexo y del tipo de consumo (con y sin consumo episódico excesivo de alcohol [CEEA], con y sin consumo de tabaco o marihuana). La muestra final, no probabilística y de carácter accidental, estuvo compuesta por 279 estudiantes universitarios (75.6% mujeres; M edad = 23.02; DE = 3.36) que completaron un cuestionario online. Se encontraron diferencias significativas en la percepción de riesgo (global y para indicadores individuales) en función del sexo y del tipo de consumo. A su vez, el sexo (i.e., ser hombre) y la mayor frecuencia de CEEA, de consumo de tabaco y marihuana se asociaron a la percepción de un menor riesgo atribuido al consumo de cada sustancia. Los hallazgos sugieren que las conductas de consumo frecuente e intensivo podrían ser el foco de intervenciones para corregir posibles sesgos en la interpretación o valoración del riesgo percibido.

Abstract Alcohol, tobacco, and marijuana consumption is highly prevalent among emerging adult college students. One of the variables influencing the consumption of these three psychoactive substances is the perception of risk associated with such behavior. This work examined bivariate and multivariate relationships between risk perception of alcohol, tobacco and marijuana use, and the use of those substances, in Argentinian emerging adults that attend college. Additionally, we analyzed differences in risk perception in regards of gender. A sample of 279 college students (75.6% women; M age = 23.02; SD = 3.36) completed an online survey. We used a non-probabilistic and accidental sampling. We found significant differences in risk perception as a function of gender and type of consumption (i.e., with/without heavy episodic drinking [HED], with or without tobacco/marijuana use). Being men and exhibiting a higher frequency of HED, tobacco or marijuana consumption were significantly associated to the perception of a lower risk attributed to each substance. These findings suggests that frequent and intensive substance use behaviors could be the focus for interventions to correct risk perceptions.

Eating-to-Cope Motives and Uncontrolled Eating as Mediators Between Negative Emotional States and Food Addiction Among Argentinean Young Adults.

Negative emotional states (NES; i.e., depression, anxiety and stress) are likely contributors to the development of food addiction (FA). The association between NES and FA symptoms may be mediated by altered eating behaviors or by eating-to-cope motives. This study examined, in a sample of Argentinean young adults, the association between NES and FA symptoms via eating-to-cope motives and three patterns of eating behaviors. We also examined whether the model was invariant across college status. The transition from high school to college is usually associated with increased exposure to stress, which promotes the probability of engaging in altered eating behaviors. A sample of 499 Argentinean young adults (mean age = 24.9 ± 3.51 years) completed a survey that assessed FA symptoms, eating behaviors (i.e., uncontrolled, emotional, and restrained eating), eating-to-cope motives and NES. A path analysis tested the indirect association between NES and FA symptoms via uncontrolled, emotional or restrained eating, or by eating-to-cope. Stress and depression symptoms were indirectly associated with FA symptoms via uncontrolled eating and eating-to-cope motives. The model was invariant across college status. The findings suggest that NES are associated with FA symptoms by increasing uncontrolled eating and eating-to-cope motives. Young adults exhibiting greater depressive or stress symptoms, higher eating-to-cope, or higher uncontrolled eating may be at risk for FA. Future research should examine the significance of this pattern by tailoring interventions to these characteristics.

Factores que diferencian el consumo frecuente y esporádico de marihuana en estudiantes universitarios / Factors differentiating frequent and sporadic marijuana use in college students

Resumen Aunque el consumo de marihuana es altamente prevalente entre universitarios de Argentina, poco se sabe respecto a los factores que permiten distinguir a los consumidores frecuentes de marihuana de quienes consumen esporádicamente. Por esta razón, en el presente trabajo se indagó sobre las posibles variaciones en los contextos de consumo, motivos de consumo, normas percibidas y estrategias conductuales de protección entre universitarios con consumo frecuente o esporádico de marihuana, y se analizó la utilidad de este conjunto de variables para distinguir entre estos los tipos de consumidores mencionados. Para ello, se contó con una muestra de 1083 estudiantes universitarios argentinos que completó una encuesta en línea sobre el consumo de sustancias. En particular, este trabajo se realizó con la submuestra que reportó consumir marihuana en los últimos 30 días (n = 158; 51.3 % mujeres). Dicha encuesta interrogaba sobre el consumo de marihuana y las consecuencias negativas asociadas, así como por motivos de consumo, normas sociales percibidas y estrategias conductuales de protección. Como resultado, los consumidores frecuentes presentaron mayor cantidad de consecuencias negativas (M = 4.92) que los consumidores esporádicos (M = 1.82; p < .05), y se halló un perfil distintivo en un conjunto de variables. A nivel multivariado, los motivos de animación (OR = 1.230; p < .05), las estrategias conductuales de protección (OR = .941; p < .05), el consumo en solitario (OR = 2.024; p < .05) y el consumo en fiestas universitarias (OR = 2.669; p < .05) discriminaron significativamente entre ambas clases de consumidores. En general, los hallazgos revelaron subpoblaciones heterogéneas de consumidores de marihuana que difieren no solo en el consumo y sus consecuencias, sino también en los contextos de consumo y en un conjunto de variables relevantes. Estas subpoblaciones distintivas requieren de intervenciones diferentes y específicas.

Abstract Although marijuana use is highly prevalent among university students in Argentina, little is known about the factors that distinguish frequent marijuana users from sporadic users. For this reason, the present study investigated the possible variations in the contexts of consumption, motives for consumption, perceived norms, and protective behavioral strategies among university students with frequent or sporadic marijuana use, and analyzed the usefulness of this set of variables to distinguish between these two types of users. For this purpose, a sample of 1083 Argentine university students completed an online survey on substance use. In particular, this work was conducted with the subsample that reported using marijuana in the last 30 days (n = 158; 51.3 % female). The survey asked about marijuana use and associated negative consequences, as well as motives for use, perceived social norms, and protective behavioral strategies. As a result, frequent users had a higher number of negative consequences (M = 4.92) than sporadic users (M = 1.82; p < .05), and a distinctive profile was found on a set of variables. At the multivariate level, cheerleading motives (OR = 1.230; p < .05), protective behavioral strategies (OR = .941; p < .05), solo use (OR = 2.024; p < .05), and college party use (OR = 2.669; p < .05) discriminated significantly between the two classes of users. Overall, the findings revealed heterogeneous subpopulations of marijuana users that differ not only in use and its consequences, but also in contexts of use and in a set of relevant variables. These distinct subpopulations require different and specific interventions.

Rewarding and Antidepressant Properties of Ketamine and Ethanol: Effects on the Brain-Derived Neurotrophic Factor and TrkB and p75NTR Receptors.

There is a high level of comorbidity between depression and alcohol use disorder. Subanesthetic doses of ketamine induce short-acting and enduring antidepressant effects after a single or a few administrations. Considering such comorbidity, we assessed, in Swiss male mice, if ketamine-induced antidepressant-like effects would alter ethanol's rewarding effects; and, if ethanol pretreatment would alter the rewarding and antidepressant effects of ketamine. The role of the brain-derived neurotrophic factor (BDNF) and its high and low affinity receptors TrkB and p75NTR, respectively, in both reward and depression-related behaviors is well established. The present study assessed, in outbred Swiss male mice, the expression of these proteins in the prefrontal cortex and hippocampus. Ketamine did not alter the development of ethanol-induced conditioned place preference (CPP), yet ethanol inhibited the expression of CPP induced by 50 mg/kg ketamine. The antidepressant action of 50 mg/kg ketamine was attenuated after repeated treatment (i.e., developed tolerance), an effect blocked by ethanol preexposure; ethanol also inhibited the antidepressant effect of 30 mg/kg ketamine. Ketamine (50 mg/kg) and Ethanol-Ketamine (50 mg/kg) groups showed lower levels of 145 kDa TrkB in the hippocampus than Saline-treated group. Ethanol-Ketamine (50 mg/kg) decreased the hippocampal expression of p75NTR compared to Saline-Saline and Saline-Ethanol groups. Ketamine (50 mg/kg) induced hippocampal downregulation of 145 kDa TrkB may contribute to ketamine-induced antidepressant tolerance. Likewise, a relationship between low hippocampal levels of p75NTR in the Ethanol-Ketamine (50 mg/kg) and ketamine-induced CPP blockade may be considered. The findings underscore potential ethanol-ketamine interactions likely to undermine ketamine putative antidepressant effects.

Factors Associated with Simultaneous or Concurrent Use of Alcohol and Marijuana in Argentina.

Background: The identification of factors promoting simultaneous alcohol and marijuana (SAM) use is important to promote early intervention efforts. The associations between impulsivity facets and SAM (or concurrent alcohol and marijuana, CAM) use have been analyzed in North American samples. These topics, however, remain unexplored in South American samples. This study assessed if internalizing symptoms, five impulsivity dimensions, and emotional regulation strategies differentiate between participants who reported last 2-month SAM use, CAM use, alcohol, or marijuana only use, or that reported no substance use. Methods: A sample of 1057 Argentinian citizens answered an online survey. A multinominal logistic regression was conducted on drug use membership. Results: Circa 25% of the sample reported SAM use. Higher sensation seeking differentiated between SAM use versus no substance use, and those with lower sensation seeking were more likely to be classified into the alcohol-only group or into the nonuse group, than into the SAM use group. Stress scores uniquely predicted membership into the alcohol-only category. Those with lower use of emotional suppression were more likely than nonusers to be classified in all drug use categories, except CAM use. Higher emotional suppression scores were associated with membership into the nonuse group or the alcohol-only group, when compared to the SAM use group. Hazardous drinking was significantly greater in SAM than in alcohol-only users. Conclusions: The study highlights the relevance of sensation seeking as a predictor of SAM use and pinpoints emotional suppression as common factor modulating hazardous drug use behaviors.

From binge eating to binge drinking: A new and robust paradigm for assessing binge ethanol self-administration in male rats.

Animal models of alcohol (ethanol) self-administration are crucial to dissect the neurobiological mechanisms underlying alcohol dependence, yet only a few of these induce pharmacologically relevant levels of alcohol consumption and rarely the alcohol self-administration co-occurs with other addictive behaviours. The present study aims to validate a novel model of voluntary ethanol consumption in male Wistar rats, in which ethanol access follows a binge eating experience. Over 10 sessions, Wistar rats were exposed to binge or control eating (i.e., the ingestion of 11.66 and 0.97 kcal/3 min, respectively, derived from a highly palatable food), immediately followed by two-bottle choice intake tests (2%, 6%, 10% or 14% w/w ethanol vs. water). Rats exposed to binge eating drank significantly more 6% or 10% (w/w) ethanol than control peers, reaching up to 6.3 gEtOH /kg. Rats stimulated with 2%, 6%, 10% or 14% ethanol after binge eating, but not those given those ethanol concentrations after control eating, exhibited significant within-group increases in ethanol drinking. This ethanol consumption was not altered by quinine adulteration (up to 0.1 g/L), and it was blocked by naltrexone (10 mg/kg), administered immediately before binge eating. Blood ethanol levels significantly correlated with ethanol consumption; and the more ethanol consumed, the greater the distance travelled in an open field test conducted after the two-bottle choice test. Altogether, this self-administration model seems a valid and robust alternative with remarkable potential for research on different stages of the alcohol addiction and, particularly, to assess interactions between alcohol consumption and others addictive-like behaviours.

Impulsividad y toma de riesgos: efecto prospectivo sobre el consumo de alcohol en adolescentes argentinos / Impulsivity and risk taking: prospective effect on alcohol consumption in Argentine adolescents

La impulsividad y la toma de riesgos son dos factores de personalidad estrechamente asociados y que han sido relacionados con el consumode alcohol. Sin embargo, son escasos los estudios que evalúan de manera longitudinal la relación de estas variables sobre el consumo de alcohol en adolescentes latinoamericanos. Esta investigación examinó, atendiendo a las diferencias en función del sexo, el efecto prospectivo dela impulsividad rasgo (Urgencia Positiva, Urgencia Negativa, Falta de Premeditación, Falta de Perseverancia y Búsqueda de Sensaciones) y latoma de riesgos sobre el consumo de alcohol en adolescentes argentinos. Participaron 953 estudiantes de 11 a 16 años al inicio del estudio(M edad= 13.31 ± 0.96; 55.2% mujeres) residentes en Córdoba capital (Argentina). Se realizaron dos recogidas de datos separadas por unperíodo de 12 meses. En la primera recolección, los participantes informaron de su consumo de alcohol durante los últimos doce meses, completaron la Prueba de Riesgo Analógico con Globos y respondieron una encuesta sobre impulsividad rasgo (Escala de impulsividad UPPS-P).En la segunda evaluación reportaron su consumo de alcohol durante el último año. En función del consumo de alcohol en los dos tiempos se losclasificó en: Abstemios, Nuevos Bebedores, Bebedores Regulares y Nuevos Abstemios. Los resultados muestran que las distintas dimensionesde la impulsividad (en particular la Búsqueda de Sensaciones), en ambos sexos, y la toma de riesgos, en mujeres, permitieron distinguir entrequienes nunca consumieron alcohol y las restantes modalidades de consumo. Los hallazgos tienen implicancias prácticas para el desarrollo deintervenciones destinadas a adolescentes con elevados niveles de impulsividad y toma de riesgos, atendiendo especialmente a las diferencias en función del sexo. (AU)

Impulsivity and risk taking are personality traits associated to alcohol use. However, there is a scarcity of longitudinal studies evaluating how these factors affect alcohol use inLatin-American adolescents. The present study aimed at identifying, separately by sex, the prospective role of trait-like impulsivity (PositiveUrgency, Negative Urgency, Lack of Premeditation, Lack of Perseverance and Sensation Seeking) and risk taking on drinking patterns inArgentinian adolescents. High school students (n= 953, M age= 13.31 ± 0.96; range= 11-16 years old; 55.2% woman) from Cordoba (Argentina) participated in the study. There were two data collections, separated by a period of, approximately, 12 months. In the first data collection, the participants reported their alcohol consumption during the last twelve months and completed the Balloon Analogue Risk Task. Theyalso completed a psychometric measure of impulsivity-like trait trait (UPPS-P Impulsivity Scale). In the second data collection, they reportedtheir alcohol consumption during the last year. Participants were categorized, based on their alcohol use across waves, as Abstainers, NewDrinkers, Regular Drinkers or Former Drinkers. The results indicate that trait-like impulsivity (particularly Sensation Seeking), in both sexes,and risk taking, in women, distinguished between the drinking categories and the Abstainers category. This information could be relevant forthe development of sex-specific interventions targeting adolescents with high levels of impulsivity and risk taking. (AU)

The Association between Distress Tolerance and Alcohol Outcomes via Internal Drinking Motives.

INTRODUCTION: Previous work suggests that college students who perceive themselves as less able to tolerate negative affect are more motivated to use alcohol to alleviate psychological distress. Recent findings also indicate that distress tolerance influences alcohol outcomes via a positive reinforcement pathway. However, results concerning the association between distress tolerance and alcohol outcomes remain inconsistent. Aim: The present study examined the association between distinctive features of distress tolerance and alcohol outcomes via internal drinking motives (i.e., coping and enhancement) in Argentinean college students. Method: From April to November 2019, a sample of 387 college students with last-month alcohol use (Mean age = 21.09 ± 4.98) completed an online survey assessing alcohol outcomes (past-month frequency of binge drinking and negative alcohol-related consequences), internal drinking motives, and four components of distress tolerance (i.e., tolerance, appraisal, absorption, and regulation). Results: The associations between specific facets of distress tolerance and drinking outcomes were atemporally mediated by coping and enhancement motives. Coping motives significantly mediated the effect of absorption and appraisal on alcohol-related problems (i.e., lower absorption and lower appraisal were associated with more problems via higher coping motives). Enhancement motives significantly mediated the effect of absorption (lower absorption was associated with greater enhancement motives) on binge drinking frequency and alcohol-related problems. Conclusions: Distress tolerance was associated with alcohol outcomes via coping and enhancement motives in this sample of Argentinean undergraduates. The ability to withstand negative affect could be a focal point of interventions to prevent the development of maladaptive patterns of drinking.

Self-control and problematic use of social networking sites: Examining distress tolerance as a mediator among Argentinian college students.

INTRODUCTION: Use of Social networking sites (SNSs) is a highly prevalent behavior worldwide and, for some individuals, its use can turn maladaptive. There has been growing interest to identify which variables are associated with problematic use of SNSs. AIM: The present study cross-sectionally examined whether the associations between different features of self-control (i.e., impulsivity-like traits, self-regulation and emotion regulation) indirectly relate to two outcomes of SNSs (hours of use and problematic use) via distress tolerance. METHODS: A sample of 509 Argentinean college students (70.3% female; Mean age = 21.15 ± 5.15) completed an online survey. RESULTS: Two significant indirect effects were found: a) higher negative urgency was associated with higher problematic use of SNSs via lower distress tolerance and b) higher self-regulation was associated with lower problematic use of SNSs via higher distress tolerance. Positive urgency, negative urgency and self-regulation had significant direct associations with problematic use of SNSs while neither component of emotion regulation was significantly associated with SNSs outcomes. No significant direct or indirect effects were found between any of the self-control features and time spent using SNSs. CONCLUSIONS: The results highlight dysfunctional self-control, particularly emotion-driven impulsivity and low self-regulation, as relevant components of maladaptive SNSs that seem to operate by decreasing the perceived capacity to tolerate negative affect. In this context, interventions targeting the development and improvement of distress tolerance abilities might have a positive impact on problematic use of SNS.