Effects of childhood trauma on BDNF and TBARS during crack-cocaine withdrawal

Objective: To evaluate the association between childhood trauma (CT) and serum levels of brain-derived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARS) during crack-cocaine withdrawal. Method: Thirty-three male crack-cocaine users were recruited at admission to a public addiction treatment unit. Serum BDNF and TBARS levels were evaluated at intake and discharge. Information about drug use was assessed by the Addiction Severity Index-6th Version (ASI-6); CT was reported throughout the Childhood Trauma Questionnaire (CTQ). CTQ scores were calculated based on a latent analysis model that divided the sample into low-, medium-, and high-level trauma groups. Results: There was a significant increase in BDNF levels from admission to discharge, which did not differ across CT subgroups. For TBARS levels, we found a significant time vs. trauma interaction (F2,28 = 6.357, p = 0.005,ηp 2 = 0.312). In participants with low trauma level, TBARS decreased, while in those with a high trauma level, TBARS increased during early withdrawal. Conclusion: TBARS levels showed opposite patterns of change in crack-cocaine withdrawal according to baseline CT. These results suggest that CT could be associated with more severe neurological impairment during withdrawal.

Ceftriaxone Attenuated Anxiety-Like Behavior and Enhanced Brain Glutamate Transport in Zebrafish Subjected to Alcohol Withdrawal.

Chronic and/or excessive consumption of alcohol followed by reduced consumption or abstention can result in Alcohol Withdrawal Syndrome. A number of behavioral changes and neurological damage result from ethanol (EtOH) withdrawal. Ceftriaxone (Cef) modulates the activity of excitatory amino acid transporters by increasing their gene expression. Zebrafish are commonly used to study alcohol exposure. The aim of this study was to evaluate the influence of Cef (100 µM) on behavior patterns, glutamate transport activity, and oxidative stress in zebrafish brains subjected to EtOH (0.3% v/v) withdrawal. The exploratory tests using Novel tank showed that EtOH withdrawal promoted a decrease in the time spent and number of entries of in the bottom displaying an anxiety-like behavior. In contrast, treatment with Cef resulted in recovery of exploratory behavioral patterns. Ceftriaxone treatment resulted in increased glutamate uptake in zebrafish subjected to EtOH withdrawal. Furthermore, EtOH withdrawal increased reactive species, as determined using thiobarbituric acid and dichlorodihydrofluorescein assays. Treatment with Cef reversed these effects. Ceftriaxone promoted a significant reduction in brain sulfhydryl content in zebrafish subjected to EtOH withdrawal. Therefore, Cef treatment in conjunction with EtOH withdrawal induced anxiolytic-like effects due to possible neuromodulation of glutamatergic transporters, potentially through mitigation of oxidative stress.

m-Trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 modulates the hippocampal neurotoxic adaptations and abolishes a depressive-like phenotype in a short-term morphine withdrawal in mice.

The opioid withdrawal syndrome is defined as a complex phenomenon involving multiple cellular adaptations, which leads to the emergence of aversive physical and affective signs. The m-trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 elicits an antidepressant-like effect by modulating the opioid system in different animal models of mood disorders. Notably, repeated exposure to (m-CF3-PhSe)2 developed neither tolerance nor withdrawal signs in mice. The aim of the present study was to investigate whether (m-CF3-PhSe)2 attenuates the physical signs and the depressive-like phenotype during morphine withdrawal through its neuroprotective effects on oxidative stress, the NMDA receptor and the proBDNF/mBDNF signaling in the hippocampus of mice. Adult Swiss mice received saline solution or escalating doses (20-100 mg/kg, sc) of morphine for six days. For the next three days, the animals were treated with canola oil, (m-CF3-PhSe)2 (5 and 10 mg/kg, ig) or methadone (5 mg/kg, sc) whereas morphine injections were discontinued. On day 9, physical withdrawal signs and depressive-like behavior were assessed 30 min after the last administration of (m-CF3-PhSe)2. Although short-term treatment with (m-CF3-PhSe)2 at both doses suppressed the aversive physical and affective signs in morphine withdrawn-mice, the highest dose of (m-CF3-PhSe)2 per se increased the teeth chattering manifestation. The intrinsic antioxidant property of (m-CF3-PhSe)2 modulated oxidative stress, it also restored the NMDA receptor levels in the hippocampus of morphine withdrawn-mice. Besides, (m-CF3-PhSe)2 downregulated the proBDNF/p-75NTR/JNK pro-apoptotic pathway without affecting the mBDNF/TrkB/ERK/CREB pro-survival signaling in the hippocampus of morphine withdrawn-mice. The results show that (m-CF3-PhSe)2 treatment modulated the hippocampal neurotoxic adaptations and abolished the depressive-like phenotype following morphine withdrawal in mice.

Effects of childhood trauma on BDNF and TBARS during crack-cocaine withdrawal.

OBJECTIVE: To evaluate the association between childhood trauma (CT) and serum levels of brain-derived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARS) during crack-cocaine withdrawal. METHOD: Thirty-three male crack-cocaine users were recruited at admission to a public addiction treatment unit. Serum BDNF and TBARS levels were evaluated at intake and discharge. Information about drug use was assessed by the Addiction Severity Index-6th Version (ASI-6); CT was reported throughout the Childhood Trauma Questionnaire (CTQ). CTQ scores were calculated based on a latent analysis model that divided the sample into low-, medium-, and high-level trauma groups. RESULTS: There was a significant increase in BDNF levels from admission to discharge, which did not differ across CT subgroups. For TBARS levels, we found a significant time vs. trauma interaction (F2,28 = 6.357, p = 0.005,ηp 2 = 0.312). In participants with low trauma level, TBARS decreased, while in those with a high trauma level, TBARS increased during early withdrawal. CONCLUSION: TBARS levels showed opposite patterns of change in crack-cocaine withdrawal according to baseline CT. These results suggest that CT could be associated with more severe neurological impairment during withdrawal.

The Network Structure of Tobacco Withdrawal in a Community Sample of Smokers Treated With Nicotine Patch and Behavioral Counseling.

INTRODUCTION: Network theories of psychopathology highlight that, rather than being indicators of a latent disorder, symptoms of disorders can causally interact with one another in a network. This study examined tobacco withdrawal from a network perspective. METHODS: Participants (n = 525, 50.67% female) completed the Minnesota Tobacco Withdrawal Scale four times (2 weeks prior to a target quit day, on the target quit day, and 4 and 8 weeks after the target quit day) over the course of 8 weeks of treatment with nicotine patch and behavioral counseling within a randomized clinical trial testing long-term nicotine patch therapy in treatment-seeking smokers. The conditional dependence among seven withdrawal symptoms was estimated at each of the four measurement occasions. Influential symptoms of withdrawal were identified using centrality indices. Changes in network structure were examined using the Network Comparison Test. RESULTS: Findings indicated many associations among the individual symptoms of withdrawal. The strongest associations that emerged were between sleep problems and restlessness, and associations among affective symptoms. Restlessness and affective symptoms emerged as the most central symptoms in the withdrawal networks. Minimal differences in the structure of the withdrawal networks emerged across time. CONCLUSIONS: The cooccurrence of withdrawal symptoms may result from interactions among symptoms of withdrawal rather than simply reflecting passive indicators of a latent disorder. Findings encourage greater consideration of individual withdrawal symptoms and their potential interactions and may be used to generate hypotheses that may be tested in future intensive longitudinal studies. IMPLICATIONS: This study provides a novel, network perspective on tobacco withdrawal. Drawing on network theories of psychopathology, we suggest that the cooccurrence of withdrawal symptoms may result from interactions among symptoms of withdrawal over time, rather than simply reflecting passive indicators of a latent disorder. Results indicating many associations among individual symptoms of withdrawal are consistent with a network perspective. Other results of interest include minimal changes in the network structure of withdrawal across four measurement occasions prior to and during treatment with nicotine patch and behavioral counseling.

O que pessoas que usam drogas buscam em serviços de saúde? Compreensões para além da abstinência / What do people who use drugs look for in healthcare services? Understanding this issue beyond abstinence / ¿Qué es lo que las personas que usan drogas buscan en los servicios de salud? Comprensiones más allá de la abstinencia

Proposições de modificação da Atenção no Sistema Único de Saúde (SUS) às pessoas que usam drogas têm desconsiderado suas necessidades, demandas e expectativas. A partir de contribuições da Saúde Coletiva, buscou-se compreendê-las por meio de pesquisa qualitativa que envolveu entrevistas semiestruturadas, grupos focais e observação participante em Centros de Atenção Psicossocial-Álcool e Drogas (Caps-AD). Constatou-se que os usuários se dirigem aos serviços não apenas para interromper o consumo de drogas, mas também para reduzi-lo, para receber atenção em relação a comprometimentos orgânicos ou psíquicos, construir laços sociais, ter acesso a condições básicas de vida e conquistar autonomia. A pesquisa, ao ampliar as compreensões sobre as demandas, necessidades e expectativas das pessoas que usam drogas, apresentou contribuições para a análise e redefinição das práticas e do modelo de atenção adotados no SUS.(AU)

Proposals to modify the care provided for drug users in the Brazilian National Health System (SUS) have not been considering their needs, demands and expectations. Based on contributions from Collective Health, our objective was to understand them by means of a qualitative research that involved semi-structured interviews, focus groups and participant observation at Alcohol and Drugs Psychosocial Care Centers (Caps AD). We found that users go to the services not only to interrupt drug use, but also to reduce it, to receive care for organic or psychological problems, to construct social bonds, to have access to basic life conditions, and to achieve autonomy. By amplifying the understanding about the demands, needs and expectations of people who use drugs, the research has contributed to the analysis and redefinition of the care practices and model adopted by SUS.(AU)

Las propuestas de modificación de la atención en el Sistema Brasileño de Salud (SUS) para las personas que usan drogas han desconsiderado sus necesidades, demandas y expectativas. A partir de contribuciones de la Salud Colectiva, se buscó comprenderlas por medio de una investigación cualitativa que envolvió entrevistas semiestructuradas, grupos focales y observación participante en Centros de Atención Psicosocial - Alcohol y Drogas (Caps AD). Se constató que los usuarios se dirigen a los servicios no solo para interrumpir el consumo de drogas, sino también para reducirlo, para recibir atención para comprometimientos orgánicos o psíquicos, construir lazos sociales, tener acceso a condiciones básicas de vida y conquistar autonomía. La investigación, al ampliar las comprensiones sobre las demandas, necesidades y expectativas de las personas que usan drogas, presentó contribuciones para el análisis y redefinición de las prácticas y del modelo de atención adoptados en el SUS.(AU)

Cognitive interference as a possible therapeutic strategy to prevent expression of benzodiazepine withdrawal.

Benzodiazepines are usually prescribed for anxiety and sleep disorders in long-term schedules that may cause drug dependence. Discontinuation after prolonged administration may lead to withdrawal expression, being anxiety the most predominant sign. The context-dependent associative learning process that underlies diazepam dependence can be interfered by pre-exposure to the drug administration context, an effect known as latent inhibition. Considering this background, the primary aim of the present investigation is to develop a therapeutic strategy to prevent diazepam withdrawal in male Wistar rats by interfering with this learning process. Nitric oxide is a crucial player in learning and memory, hippocampal synaptic transmission and in diazepam withdrawal. Then, a secondary goal is to determine how latent inhibition could alter functional plasticity and neuronal nitric oxide synthase enzyme (NOS-1) expression within the hippocampus, by using multi-unitary cell recordings and Western blot, respectively. Our results indicate that chronic diazepam treated animals under latent inhibition did not show anxiety, or changes in hippocampal synaptic transmission, but a significant reduction in NOS-1 expression was observed. Accordingly, pharmacological NOS-1 inhibition resembles behavioral and electrophysiological changes induced by latent inhibition. Contrary, diazepam treated animals under Control protocol expressed anxiety and evidenced an increased hippocampal-plasticity, without alterations in NOS-1 expression. In conclusion, manipulation of the contextual cues presented during diazepam administration may be considered as an effective non-pharmacological tool to prevent the withdrawal syndrome. This behavioral strategy may influence hippocampal synaptic transmission, probably by alterations in nitric oxide signaling pathways in this structure.

Resistance to fear memory destabilization triggers exaggerated emotional-like responses following memory reactivation.

Fear memory reactivation does not always lead to memory destabilization-reconsolidation. For instance, fear memories formed following withdrawal from chronic ethanol consumption or a stressful event are less likely to become destabilized after reactivation, with the effect of recall of these memories on the affective state still requiring elucidation. Here, we investigated the negative emotional-like responses following fear memory reactivation in ethanol-withdrawn (ETOH) rats by focusing on the possible role played by destabilization. Our findings indicated that ETOH rats displayed an increased freezing in a novel context and an anxiogenic-like response in the elevated plus maze (EPM) following memory reactivation, whereas the behavior of CON animals was not affected. The destabilization blockade by pre-reactivation nimodipine (16 mg/kg, s.c) administration promoted in CON animals a similar behavior in the EPM and in a novel environment as that exhibited by ETOH rats after the reminder. Moreover, facilitating destabilization by pre-reactivation d-cycloserine (5 mg/kg, i.p) administration prevented the emotional-like disturbances observed in ETOH rats. Finally, using restraint stress, which is also an inductor of a fear memory resistant to destabilization, an increased fear response in an unconditioned environment and an anxiogenic-like state was also found after the presentation of the fear reminder in stressed rats. Our results suggest that, in the context of resistant fear memories, the occurrence of destabilization influences how animals respond to subsequent environmental challenges following reactivation.

Cognitive functions of subjects with cocaine and crack dependency disorder during early abstinence. / Funcionamiento cognitivo en sujetos con trastorno de dependencia a cocaina y crack durante la abstinencia temprana.

INTRODUCTION: Cognitive effects caused by cocaine and crack consumption, especially deficits in executive functions may increase the likelihood of drug-seeking behaviour and interfere with the ability of users to assimilate and participate in rehabilitation programs. AIM: To determine in early abstinence the state of executive functions, the impulsiveness and craving in cocaine and crack consumers. SUBJECTS AND METHODS: This cross-sectional study functions, with a sample of 60 male aged between 31.38 ± 7.26 years old, distributed in three groups: inhaled cocaine users (CDP-I; n = 15), with 23.13 ± 7.2 age of onset of consumption; crack cocaine users (CDP-C; n = 26), with 20.81 ± 4.21 age of onset of consumption, and a control groups of no-addiction individuals (n = 19). Sociodemographic, clinical and cognitive assessments were applied. RESULTS: The data showed that significant differences in socioeconomic level score and impulsiveness. Consumer groups have with lower scores with respect the control group. CDP-C group showed poor performances compared to the CDP-I and control groups, in the Berg Test, Tower of London, numbers in the direct order and subtraction. CDP-I group showed less score in planning compare with the other two groups. CONCLUSIONS: In early abstinence crack users manifest a greater number of deficits, mainly in working memory, planning and cognitive flexibility.

TITLE: Funcionamiento cognitivo en sujetos con trastorno de dependencia a cocaina y crack durante la abstinencia temprana.Introduccion. Los efectos cognitivos causados por el consumo de cocaina y crack, especialmente los deficits de las funciones ejecutivas, aumentan la probabilidad de un comportamiento de busqueda de drogas e interfieren en la capacidad de los usuarios de asimilar y participar en los programas de rehabilitacion. Objetivo. Determinar en la abstinencia temprana el estado de las funciones ejecutivas, la impulsividad y la ansiedad (craving) en consumidores de cocaina y crack. Sujetos y metodos. Este estudio transversal tuvo una muestra de 60 hombres, con una edad media de 31,38 ± 7,26 años, distribuidos en tres grupos: usuarios que inhalan cocaina (CDP-I; n = 15), con una edad de inicio de consumo de 23,13 ± 7,2 años; consumidores de cocaina en crack (CDP-C; n = 26), con una edad de inicio de consumo de 20,81 ± 4,21 años, y un grupo control de sujetos sin adiccion (n = 19). Se aplicaron evaluaciones sociodemograficas, clinicas y cognitivas. Resultados. Los datos mostraron diferencias significativas en las puntuaciones del nivel socioeconomico e impulsividad. Los grupos de consumidores tienen puntuaciones mas bajas con respecto al grupo control. El grupo CDP-C mostro rendimientos pobres en comparacion con el grupo CDP-I y el grupo control en las pruebas de Berg, torre de Londres, numeros en orden y sustraccion directos. El grupo CDP-I mostro una menor puntuacion en la planificacion comparada con los otros dos grupos. Conclusiones. En la abstinencia temprana, los consumidores de crack manifiestan mayor numero de deficits, principalmente en la memoria de trabajo, la planificacion y la flexibilidad cognitiva.

Modafinil reduces amphetamine preference and prevents anxiety-like symptoms during drug withdrawal in young rats: Involvement of dopaminergic targets in VTA and striatum.

Drug abuse and addiction are overwhelming health problems mainly during adolescence. Based on a previous study of our research group, the rats that received modafinil (MD) during the adolescence showed less preference for amphetamine (AMPH) in adulthood. Our current hypothesis is that MD will show beneficial effects against AMPH preference and abstinence symptoms during adolescence, a critical lifetime period when drug hedonic effects are more pronounced. We investigated the influence of MD pretreatment on AMPH preference in conditioned place preference (CPP) paradigm in adolescent rats and anxiety-like symptoms during drug withdrawal (48 h after the last AMPH dose) in elevated plus maze (EPM) task. Besides that, oxidative and molecular status were evaluated in the ventral tegmental area (VTA) and striatum. Our findings showed, as it was expected, that adolescent animals developed AMPH preference together with anxiety-like symptoms during the drug withdrawal while the MD pretreatment prevented those behaviors. Besides promoting benefits on reward parameters, MD was able to preserve VTA and striatum from oxidative damages. This was observed by the increased catalase activity and reduced generation of reactive species and lipid peroxidation, which were inversely modified by AMPH exposure. At molecular level, MD exerted an interesting modulatory activity on the VTA and induced an up-regulation in striatal dopaminergic targets (TH, DAT, D1R and D2R). So far, during the adolescence, MD presented beneficial behavioral outcomes that could be attributed to its modulatory activity on the striatal dopaminergic system in an attempt to maintain the adequate dopamine levels.

Ethanol withdrawal limits fear memory reactivation-induced molecular events associated with destabilization phase: Influence of d-cycloserine.

A 1-day fear memory in ethanol withdrawn (ETOH) rats is resistant to destabilization-reconsolidation process. However, d-cycloserine (DCS) reverts this disturbance. Considering that the formation of pathological fear memories in humans often occurs long time before the requirement of an intervention, the study of older memories is relevant in ETOH rats. In addition, the resistance to destabilization and DCS effect on this memory phase at molecular level in ETOH rats have not been corroborated yet. Firstly, we examined the effect of a pharmacological intervention after reactivation on reconsolidation of a 7-day fear memory in ETOH rats. Then, and considering that enhanced GluN2B expression and ubiquitin-proteasome system (UPS) activity are involved in destabilization, we evaluated them following reactivation in ETOH rats. Furthermore, DCS effect on such destabilization markers was examined. It was found that the pharmacological intervention after reactivation did not affect the 7-day fear memory in ETOH rats with DCS reversing this resistance. Memory reactivation increased GluN2B expression, polyubiquitination levels and proteasome activity in the basolateral amygdala complex (BLA) of control (CON) rats only; without affecting these molecular events in ETOH rats. Finally, ETOH rats treated with DCS and CON animals displayed elevated and similar UPS activities in the BLA after reactivation. In conclusion, the reactivation of an older fear memory formed during ethanol withdrawal does not trigger the molecular events associated with destabilization, and DCS facilitates this memory phase by enhancing the UPS activity.

Lifelong exposure to caffeine increases anxiety-like behavior in adult mice exposed to tobacco smoke during adolescence.

Caffeine and tobacco smoke are among the most frequently self-administered licit psychoactive drugs in the world. Both drugs affect anxiety levels, however, little is known on the impact of the dual exposure in the adolescent brain, the period during which smoking begins. Considering that anxiety is a relevant factor for smoking maintenance and relapse, we investigated the effects of lifelong exposure to caffeine on anxiety levels of Swiss mice exposed to tobacco smoke during adolescence. Caffeine was administrated during all prenatal and postnatal life (CAF, 0.1 g/l to drink). From postnatal day 30-45, animals were exposed to tobacco smoke (SMK, whole body exposure, 8 h/day) generated from research cigarettes type 3R4F (nicotine = 0.73 mg/per cigarette). Four groups were analyzed: (1) CAF + SMK exposure; (2) SMK exposure; (3) CAF exposure; (4) Control. Anxiety levels were assessed in the elevated plus maze at the end of smoke exposure (PN45), at short- (PN55) and long-term (PN75) withdrawal. Caffeine exposure reduced decision making time (time in center of maze) during adolescence (PN45 and PN55). In addition, caffeine increased anxiety-like behavior during long-term tobacco smoke withdrawal. The present study provides experimental evidence that caffeine and tobacco smoke during adolescence interact resulting in emotional dysregulation during tobacco smoke withdrawal. Particularly, increased anxiety-like behavior during long-term withdrawal in CAF + SMK animals demonstrates late-emergent effects. In this sense, our data suggest that lifelong caffeine exposure may be an important factor in tobacco relapse.

A Mixed-Method Analysis of Persisting Effects Associated with Positive Outcomes Following Ibogaine Detoxification.

We examined persisting effects, self-perceived challenges, and potential benefits associated with positive outcomes following ibogaine detoxification using data collected as part of a larger online retrospective study of 73 patients who received treatment for chronic opioid use in Mexico between 2012 and 2015. A mixed-methods design was used comparing treatment responders versus non-responders, as well as content coding of themes from open-ended questions. Most participants reported positive persisting effects of ibogaine detoxification (e.g., enhanced personal sense of gratitude and authenticity, and meaning and appreciation for life). Compared to non-responders, treatment responders endorsed greater persisting changes in their ability to tolerate difficult/painful feelings, capacity for coping with stress, and reduced unhealthy anger. Treatment responders reported greater change in subjective levels of inner peace, joy, feelings of love/openheartedness, and experiences of sacredness in life. Qualitative analyses revealed that treatment responders reported a heightened sense of spiritual awareness and greater connection to their intra-/interpersonal relationships after ibogaine detoxification. Notable challenges of ibogaine detoxification included psychological and health-related difficulties during treatment and challenges with post-treatment integration. Findings highlight the persisting effects associated with positive response to ibogaine detoxification and possible post-treatment needs (i.e., more integration/aftercare resources). Future research using rigorous experimental designs is needed.

Behavioral and biochemical effects of ethanol withdrawal in zebrafish.

Chronic alcohol use induces adaptations and toxicity that can induce symptoms of anxiety, autonomic hyperarousal, and epileptic seizures when alcohol is removed (withdrawal syndrome). Zebrafish has recently gained wide attention as a behavioral model to study the neurobehavioral effects of acute and chronic alcohol use, including withdrawal. The literature, however, is very contradictory on findings regarding withdrawal effects, with some studies reporting increased anxiety, while others report no effect. A meta-analytic approach was taken to find the sources of this heterogeneity, and ethanol concentration during exposure and exposure duration were found to be the main sources of variation. A conceptual replication was also made using continuous exposure for 16 days in waterborne ethanol (0.5%) and assessing anxiety-like behavior in the light/dark test after 60 min withdrawal. Withdrawal was shown to reduce preference for darkness, consistent with decreased anxiety, but to increase risk assessment, consistent with increased anxiety. Animals were also subjected to the withdrawal protocol and injected with pilocarpine in a sub-convulsive dose to assess susceptibility to epileptic seizure-like behavior. The protocol was sufficient to increase susceptibility to epileptic seizure-like behavior in animals exposed to ethanol. Finally, withdrawal also decreased catalase activity in the brain, but not in the head kidney, suggesting mechanisms associated with the behavioral effects of ethanol withdrawal.

Glucocorticoid receptor gene modulates severity of depression in women with crack cocaine addiction.

Crack cocaine addicted inpatients that present more severe withdrawal symptoms also exhibit higher rates of depressive symptoms. There is strong evidence that the identification of genetic variants in depression is potentialized when reducing phenotypic heterogeneity by studying selected groups. Since depression has been associated to dysregulation of the hypothalamic-pituitary-adrenal axis, this study evaluated the effects of SNPs in stress-related genes on depressive symptoms of crack cocaine addicts at early abstinence and over the detoxification treatment (4th, 11th and 18th day post admission). Also, the role of these SNPs on the re-hospitalization rates after 2.5 years of follow-up was studied. One hundred eight-two women were enrolled and eight SNPs in four genes (NR3C2, NR3C1, FKBP5 and CRHR1) were genotyped. A significant main effect of NR3C1-rs41423247 was found, where the C minor allele increased depressive symptoms at early abstinence. This effect remained significant after 10,000 permutations to account for multiple SNPs tested (P=0.0077). There was no effect of rs41423247 on the course of detoxification treatment, but a slight effect of rs41423247 at late abstinence was detected (P=0.0463). This analysis suggests that the presence of at least one C allele is worse at early abstinence, while only CC genotype appears to increase depressive symptoms at late abstinence. Also, a slight effect of rs41423247 C minor allele increasing the number of re-hospitalizations after 2.5 years was found (P=0.0413). These findings are in agreement with previous studies reporting an influence of rs41423247 on sensitivity to glucocorticoids and further elucidate its resulting effects on depressive-related traits.

[Frontal symptoms, self-perceived stress, and subjective memory complaints in substance abusers]. / Sintomatología frontal, estrés autopercibido y quejas subjetivas de memoria en adictos a sustancias.

INTRODUCTION: Substance addiction is a public health problem considering that every day increases the number of individuals with problem drug use, in this sense it is interesting the study of neuropsychological variables to understand the nature of addiction, understanding that brain circuits are involved in the establishment, maintenance and rehabilitation of the same. AIMS: To determine the influence of addiction on the frontal symptoms, self-perceived stress and subjective memory complaints, secondly, to analyze how these variables relate to people with addictions and finally, establish differences in them between addicts with and without subjective memory complaints. SUBJECTS AND METHODS: ISP, EEP-14 and MFE-30 instruments were applied to a sample of 115 substance abusers, and 115 people from non-clinical population, matched for age, sex and educational level. RESULTS: Significant differences are evident between addicted to substances and non-clinical subjects in the emotional scale ISP and MFE-30, also in the clinical sample highly significant correlations between all scales are observed; Finally, among people with addictions who reported memory complaints and those who do not, significant differences are evident on all scales except for the self-perceived stress. CONCLUSIONS: It is considered necessary to take into account the levels of self-perceived stress, frontal symptoms and subjective memory complaints in substance abusers, because the executive, attentional and mnemonic problems may affect several variables in the process of treatment and rehabilitation.

TITLE: Sintomatologia frontal, estres autopercibido y quejas subjetivas de memoria en adictos a sustancias.Introduccion. La adiccion a sustancias representa un problema de salud publica, teniendo en cuenta que a diario aumenta el numero de individuos que consumen drogas. Resulta de interes el estudio de variables neuropsicologicas que permitan comprender la naturaleza de las adicciones, entendiendo que los circuitos cerebrales estan implicados en su establecimiento, mantenimiento y rehabilitacion. Objetivos. Determinar la influencia de la adiccion sobre la sintomatologia frontal, el estres autopercibido y las quejas subjetivas de memoria; analizar como se relacionan dichas variables en las personas con adicciones y establecer diferencias en cuanto a estas variables entre adictos con y sin quejas subjetivas de memoria. Sujetos y metodos. Se aplico el inventario de sintomas prefrontales (ISP), la escala de estres percibido (EEP-14) y el cuestionario de fallos de memoria de la vida cotidiana (MFE-30) a una muestra compuesta por 115 adictos a sustancias y 115 personas de poblacion no clinica, igualadas en edad, sexo y nivel educativo. Resultados. Se evidencian diferencias significativas entre los adictos a sustancias y los sujetos no clinicos en la escala emocional del ISP y el MFE-30; ademas, en la muestra clinica se observan correlaciones altamente significativas entre todas las escalas. Entre las personas con adicciones que manifestaron quejas de memoria y quienes no, se evidencian diferencias significativas en todas las escalas, a excepcion del estres autopercibido. Conclusiones. Se considera necesario tomar en cuenta los niveles de estres autopercibido, la sintomatologia frontal y las quejas subjetivas de memoria en adictos a sustancias, debido a que los problemas ejecutivos, atencionales y mnesicos podrian afectar diversas variables en el proceso de tratamiento y rehabilitacion.

Relationship between central behavioral effects and peripheral sympathetic neurotransmission functionality during acute cocaine withdrawal syndrome in adult rats.

BACKGROUND: Acute cocaine withdrawal syndrome (ACWS) is characterized as a set of organic alterations triggered by abrupt discontinuation of chronic cocaine consumption, usually occurring at 24-40 hours after withdrawal. However, little is known about the relationship between central and peripheral sympathetic neurotransmission during ACWS. OBJECTIVE AND METHODS: We investigated the mechanisms involved in central and peripheral sympathetic neurotransmission and how ACWS affects the sympathetic functionality. Cocaine was administered twice daily for 5 days in Wistar rats (at least 5 in each group): on the first and second day, 15 mg/kg/i.p.; third day, 20 mg/kg/i.p.; and finally in the last two days, 30 mg/kg/i.p. Subsequently, at 1, 24, 48 and 120 h after cocaine administration the following experiments were done: (i) at the central level, behavioral tests of open-field and elevated plus maze; and (ii) at the peripheral level, tests of catecholamine release, function of α2-adrenergic receptors (α2-ARs), imidazoline receptors (I(1,2)-Rs), L-type voltage-gated (Ca(v1.2)) Ca(2+) channels and α1-ARs. RESULTS: During ACWS, rats showed hypolocomotion and exacerbation of anxiogenic-effects 24 h after cocaine withdrawal. Likewise, a decrease in the catecholamine release and activity of α2-ARs/I(1,2)-Rs at 24-48 h after cocaine withdrawal was observed. A decrease in Ca(v1.2) channels and α1-ARs function at 48 h after cocaine withdrawal was observed. CONCLUSIONS: The relationship of central and peripheral sympathetic neurotransmission during ACWS possibly due to a failure in activation and/or inactivation of presynaptic α2-ARs/I(1,2)-Rs, may offer a potential target for attenuating ACWS.

Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol.

Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30-35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a "three-bottle choice" paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol

Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30-35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a "three-bottle choice" paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.