Developing Substance Use Research Articles

Trauma, Resilience, and Substance Use in Adolescents: A Review Article

Background: Adolescence is a sensitive phase of human life featuring changes in physical, emotional, and social characteristics. Many teens experience stressful events and trauma, which can affect their mental health and increase their risk of initiating and continuing substance use. Genetic vulnerabilities impact this relationship. In the face of trauma, while some adolescents are vulnerable, others navigate similar experiences differently, show resilience, and generally fare better without developing substance use problems. Understanding the multiple contributory factors that impact this relationship is critical in informing clinical approaches and program development. Objective: To describe the intricate dynamics between trauma, resilience, and substance abuse among adolescents. This review attempts to offer a synopsis that clarifies existing perspectives on trauma and substance use in adolescents while indicating areas for future research, clinical, and intervention programs in this critical area of adolescent well-being. Methods: A literature review was conducted to reveal available studies related to trauma, adolescent substance use, and resilience. Synthesis of findings from empirical studies, a detailed discussion on trauma and developmental factors while also addressing resilience elements alongside patterns of substance use is presented. Conclusion: Trauma, resilience, and substance use are linked in a tri-directional relationship, which is complex and dynamic. Adolescents with trauma are at higher risk of initiating and continuing substance. Resilience impacts treatment-seeking and engagement and may reduce relapse risk. Future research recommendations include improving the cultural sensitivity of interventions, studying the effects of marginalized identities, and ensuring rigorous evaluation of and progressive development of intervention programs. Results: The review highlights the bidirectional connections between trauma and substance use in adolescents. We include the consideration of resilience in adolescent responses to trauma. Resilience may reduce the risk of substance use, improve treatment-seeking and engagement in the treatment of SUD in adolescents, and reduce the risk of relapse, thereby suggesting it is a third dimension in the relationship between trauma and substance use. This review also provides evidence-based interventions and policies that are tailored to the specific needs of a diverse population of adolescents. We uncover the gaps in research, especially regarding cultural specifics and intersectionality among marginalized identities.

A Preliminary Investigation of a Conceptual Model Describing the Associations Between Childhood Maltreatment and Alcohol Use Problems

Background/Objectives: Childhood maltreatment has been linked to numerous adverse outcomes in adulthood, including problem substance use. However, not all individuals exposed to childhood maltreatment develop substance use problems, indicating the role of other factors in influencing this outcome. Past work suggests that adverse early life experiences, including childhood maltreatment, lead to neurobiological changes in frontolimbic functions that, in turn, result in altered stress and reward responses, heightened impulsivity, affect dysregulation, and, ultimately, increased risk for maladaptive behaviors such as substance use. The aim of this preliminary investigation using cross-sectional data was to test associations between these factors in the relationship between childhood maltreatment and alcohol use problems in a sample of emerging adults. Methods: Emerging adults (18–30 years old) who identified as regular drinkers (i.e., drinking at least 2–4 times in the past month) were recruited from a crowd-sourcing platform (Prolific) as well as community samples. Participants completed online standardized questionnaires assessing reward sensitivity and responsiveness, impulsivity, emotion regulation, and alcohol consequences. Results: Path analyses demonstrated good fit for the data (SRMR = 0.057, RMSEA = 0.096, 90% CI [0.055, 0.142], CFI = 0.957). Childhood maltreatment was associated with reward responsiveness (β = −0.026, Z = −4.222, p < 0.001) and emotion dysregulation (β = 0.669, Z = 9.633, p < 0.001), which in turn was associated with urgency and, subsequently, alcohol consequences (β = 0.758, Z = 7.870, p < 0.001). Conclusions: Although these findings are preliminary, the current study is one of the first to test a comprehensive model addressing the relationship between childhood maltreatment and alcohol use problems. The findings have the potential to inform treatment strategies that target motivation and goal-directed action for reducing and managing consequences associated with childhood maltreatment. Future research should test the model using longitudinal data to address the limitations of a cross-sectional study and assess temporal associations between constructs.

Social influence on drug use and sexual behaviors among rural LGBTQ+ individuals

ABSTRACT Background: Traveling to meet sexual partners and substance use are associated with increased risk of infectious disease. It is important to understand what factors may increase substances use or increased infection transmission risk (IITR) sexual behaviors among rural LGBTQ+ individuals. Objective: This study investigates substance use and sexual behaviors associated with increased infection transmission risk among rural LGBTQ+ individuals, and how these are associated with relationship type (friends or romantic partners) and travel distance. Methods: Participants (18 years+, identify as LGBTQ+, and provided a $25 gift card) were recruited from Illinois (25 counties), in 2021. Data included demographics, sexual and drug use behaviors, and assessed how these behaviors varied by relationship type and distance traveled (e.g. when meeting friends out-of-state). Results: The 398 participants were 79.1% White and 12.3% Black. By orientation, 29% heterosexual, 36% gay/lesbian, and 35% bisexual/other. By identity, 43% cisgender male, 51% cisgender female, and 6% genderqueer/other. Alcohol use while visiting out-of-state friends was more frequent among transgender (vs cisgender men; OR = 9.686, 95% confidence interval = 2.123-44.19), and individuals traveling > 1/month (all p < .050). Infection-related sexual behaviors while visiting out-of-state romantic partners was more frequent among prescription medication misuse (all p < .050) and traveling > 1/week (vs < 1/month; OR = 3.399, 95% CI = 1.037-11.144). Conclusion: This study of rural LGBTQ+ identified that alcohol use was associated with travel to visit out-of-state romantic partners, and prescription medication misuse increased infection-related sexual behavior during out-of-state travel. Health professionals can develop substance use and increased infection transmission risk sexual behavior interventions on gender minority groups in rural areas and target those who are traveling.

MODELING A REHAB–RECOVERY–RELAPSE CYCLE WITH COMMUNITY DEPENDENCE VIA ODES

In this paper, we introduce a rehab–recovery–relapse cycle model to study the interaction between healthy individuals, individuals that might develop substance use disorders (SUD), which for simplicity here we will call susceptible individuals, individuals with SUD, and individuals recovered in a rehab community. We measure the community’s health through a system defined by four non-linear ordinary differential equations in which we include a rehab community. After computing the SUD-free and coexistence equilibrium points, we find the feasibility and stability conditions of an equivalent and reduced system obtained by nondimensionalizing the equations of the original model. We have numerically investigated the importance of the parameter values on the model’s outcome via a one- and two-strain parameter analysis. From the numerical results, we observe that an efficient rehab community can be characterized by (i) a high recovery rate (the individuals stay in that community as little time as possible) and (ii) permanent rehabilitation being preferred at the expense of a low recovery rate.

Disrupted Circadian Rhythms and Substance Use Disorders: A Narrative Review.

Substance use disorder is a major global health concern, with a high prevalence among adolescents and young adults. The most common substances of abuse include alcohol, marijuana, cocaine, nicotine, and opiates. Evidence suggests that a mismatch between contemporary lifestyle and environmental demands leads to disrupted circadian rhythms that impair optimal physiological and behavioral function, which can increase the vulnerability to develop substance use disorder and related problems. The circadian system plays an important role in regulating the sleep-wake cycle and reward processing, both of which directly affect substance abuse. Distorted substance use can have a reciprocal effect on the circadian system by influencing circadian clock gene expression. Considering the detrimental health consequences and profound societal impact of substance use disorder, it is crucial to comprehend its complex association with circadian rhythms, which can pave the way for the generation of novel chronotherapeutic treatment approaches. In this narrative review, we have explored the potential contributions of disrupted circadian rhythms and sleep on use and relapse of different substances of abuse. The involvement of circadian clock genes with drug reward pathways is discussed, along with the potential research areas that can be explored to minimize disordered substance use by improving circadian hygiene.

Childhood-onset type 1 diabetes and subsequent adult psychiatric disorders: a nationwide cohort and genome-wide Mendelian randomization study

Childhood-onset type 1 diabetes (T1D) is associated with substantial psychiatric morbidity in later life, but it remains unknown whether these associations are due to common underlying biological mechanisms or the impacts of living with the condition and its treatment. Here, using Czech national register data, we identified children with T1D aged ≤14 years between 1994 and 2007 and estimated the risk of psychiatric disorders up to 24 years later. We found that children diagnosed with T1D had an elevated risk of developing substance use, mood, anxiety and personality disorders, and behavioral syndromes. Conversely, we found that children with T1D had a lower risk of developing psychotic disorders. In Mendelian randomization analysis, we found an association with schizophrenia, which, however, did not persist following multiple testing adjustment. The combined observational and Mendelian randomization evidence suggests that T1D diagnosis in childhood predisposes to far-reaching, extensive psychiatric morbidity, which is unlikely to be explicable by common underlying biological mechanisms. The findings of this study highlight that monitoring and addressing the mental health needs of children with T1D is imperative, whereas glucose dysregulation and/or inflammation implicated in schizophrenia pathogenesis warrants future research.

Building on Strong Foundations: Deploying Enhanced Replicating Effective Programs for evidence-based prevention curriculum adaptation.

Schools frequently adopt new interventions for each new public health issue, but this is both time- and resource-intensive. Adversity exposure is an example of a pervasive public health issue that emerged during Coronavirus Disease 2019 (COVID-19) with notable consequences, including an elevated risk of developing substance use disorders and mental illnesses. Adapting existing, universal, evidence-based interventions, such as the Michigan Model for HealthTM (MMH), by incorporating trauma-sensitive content is a promising approach to meet this need. We examined critical steps in promoting MMH adaptability as part of the Enhanced REP (Replicating Effective Programs) implementation strategy during the COVID-19 pandemic. We share usability testing from the 2020 to 2021 school year and describe how we apply the results to inform the group randomized trial pilot study. We applied key steps from implementation adaptation frameworks to integrate trauma-sensitive content as COVID-19 unfolded, documenting the process through field notes. We conducted initial usability testing with two teachers via interviews and used a rapid qualitative analysis approach. We conducted member checking by sharing the information with two health coordinators to validate results and inform additional curriculum refinement. We developed an adapted MMH curriculum to include trauma-sensitive content, with adaptations primarily centered on adding content, tailoring content, substituting content, and repeating/reinforcing elements across units. We designed adaptations to retain the core functional elements of MMH. Building foundational relationships and infrastructure supports opportunities to user-test intervention materials for Enhanced REP that enhance utility and relevance for populations that would most benefit. Enhanced REP is a promising strategy to use an existing evidence-based intervention to meet better the needs of youth exposed to adversity. Building on the foundations of existing evidence-based interventions, is vital to implementation success and achieving desired public health outcomes.

Addiction neurobiologists should study resilience

The study of addiction has historically focused on identifying the differences which make susceptible individuals fall prey to drug use and abuse. This has resulted in a deep understanding of the learning, reward, and habit-formation circuits which drive initial drug reinforcement, as well as exploration of the cognitive control and anxiety systems which are important for craving and relapse to drug use. However, most human drug users and a smaller proportion of laboratory animals are resilient to addiction, meaning that they can use addictive drugs without developing substance use disorders. Evidence from the neurobiology of resilience in stress models suggests that the mechanisms of resilience are distinct from those of vulnerability, and thus may be missed if resilience is not investigated in a targeted manner. In this review, we briefly review the limitations in our knowledge which have resulted from a focus on addiction vulnerability. We next introduce the formal construct of resilience and its historical application in neurobiology and clinical research. Finally, we present evidence for the presence of resilience mechanisms in studies of addiction neuroscience and argue for an increase in the focused study of resilience to substance abuse. By intentionally identifying compensatory resilience mechanisms in addiction, rather than only focusing on mechanisms of susceptibility, more effective therapeutic approaches may be discovered.

Sex Differences in Psychopathology Following Potentially Traumatic Experiences

Various psychopathology may follow trauma; however, sex differences in these ranging manifestations of posttraumatic psychopathology remain understudied. To investigate sex-specific incidence of posttraumatic psychopathology. This population-based cohort study of Danish national health registries included a cohort of individuals who experienced a potentially traumatic event (PTE) from 1994 to 2016. Individuals were further categorized by presence of any pretrauma psychopathology. A comparison group of individuals who experienced a nontraumatic stressor (nonsuicide death of a first-degree relative) was examined as a reference cohort. At least 1 of 8 PTEs (eg, physical assault, transportation accident) derived through health registry International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, with additional qualifiers to improve classification accuracy. Incidence of 9 categories of ICD-10 psychiatric disorders recorded in registries within 5 years of PTEs. The standardized morbidity ratios (SMRs) for psychopathology outcomes were also calculated to compare individuals experiencing PTEs with those experiencing a nontraumatic stressor. This study included 1 398 026 individuals who had been exposed to trauma (475 280 males [34.0%]; 922 750 females [66.0%]). The group of males who had been exposed to trauma were evenly distributed across age, while most females in the trauma-exposed group were aged 16 to 39 years (592 385 [64.2%]). Males and females were equally distributed across income quartiles and predominantly single. Following PTEs, the most common diagnosis was substance use disorders for males (35 160 [7.4%]) and depressive disorders for females (29 255 [3.2%]); incidence proportions for these and other disorders were higher among males and females with any pretrauma psychopathology. Certain PTEs had elevated onset of various psychiatric disorders and some sex differences emerged. Following physical assault, associations were found with schizophrenia or psychotic disorders for males (SMR, 17.5; 95% CI, 15.9-19.3) and adult personality disorders for females (SMR, 16.3; 95% CI, 14.6-18.3). For noninterpersonal PTEs, males had larger SMRs for substance use, schizophrenia or psychotic disorders, and adult personality disorders (SMR, 43.4; 95% CI, 41.9-45.0), and females had larger SMRs for depressive disorders (SMR, 19.0; 95% CI, 18.6-19.4). Sex differences were also observed, particularly when considering pretrauma psychopathology. For example, among interpersonal PTEs, males were most likely to develop substance use disorders after physical assault, whereas females were more likely to develop various disorders, with stronger associations seen for females without pretrauma psychiatric diagnoses. Among noninterpersonal PTEs, exposure to toxic substance showed robust associations with psychopathology, particularly in those without pretrauma psychopathology, with sex-specific differences across psychiatric categories. Mental disorders after trauma were wide-ranging for males and females, and sex differences in patterns of posttraumatic psychopathology were more pronounced when accounting for pretrauma psychopathology. Findings provide new insights for sex-relevant PTEs and their mental health consequences. It also outlines future directions for advancing understanding of a constellation of posttraumatic psychopathology in males and females.

Pleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders.

Individuals suffering from chronic pain develop substance use disorders (SUDs) more often than others. Understanding the shared genetic influences underlying the comorbidity between chronic pain and SUDs will lead to a greater understanding of their biology. Genome-wide association statistics were obtained from the UK Biobank for multisite chronic pain (MCP, Neffective = 387,649) and from the Million Veteran Program and the Psychiatric Genomics Consortium meta-analyses for alcohol use disorder (AUD, Neffective = 296,974), cannabis use disorder (CanUD, Neffective = 161,053), opioid use disorder (OUD, Neffective = 57,120), and problematic tobacco use (PTU, Neffective = 270,120). SNP-based heritability was estimated for each of the traits and genetic correlation (rg) analyses were performed to assess MCP-SUD pleiotropy. Bidirectional Mendelian Randomization analyses evaluated possible causal relationships. Finally, to identify and characterize individual loci, we performed a genome-wide pleiotropy analysis and a brain-wide analysis using imaging phenotypes available from the UK Biobank. MCP was positively genetically correlated with AUD (rg = 0.26, p = 7.55 × 10-18), CanUD (rg = 0.37, p = 8.21 × 10-37), OUD (rg = 0.20, p = 1.50 × 10-3), and PTU (rg = 0.29, p = 8.53 × 10-12). Although the MR analyses supported bi-directional relationships, MCP had larger effects on AUD (pain-exposure: beta = 0.18, p = 8.21 × 10-4; pain-outcome: beta = 0.07, p = 0.018), CanUD (pain-exposure: beta = 0.58, p = 2.70 × 10-6; pain-outcome: beta = 0.05, p = 0.014) and PTU (pain-exposure: beta = 0.43, p = 4.16 × 10-8; pain-outcome: beta = 0.09, p = 3.05 × 10-6) than the reverse. The genome-wide analysis identified two SNPs pleiotropic between MCP and all SUD investigated: IHO1 rs7652746 (ppleiotropy = 2.69 × 10-8), and CADM2 rs1248857 (ppleiotropy = 1.98 × 10-5). In the brain-wide analysis, rs7652746 was associated with multiple cerebellum and amygdala imaging phenotypes. When analyzing MCP pleiotropy with each SUD separately, we found 25, 22, and 4 pleiotropic variants for AUD, CanUD, and OUD, respectively. To our knowledge, this is the first large-scale study to provide evidence of potential causal relationships and shared genetic mechanisms underlying MCP-SUD comorbidity.

Impact of social determinants of health and individual characteristics on substance use disorder treatment utilization among emerging adults aged 18-25

Background Emerging adulthood (typically ages 18–25) is a developmental period associated with increased likelihood of developing substance use disorders (SUDs) resulting in life-altering negative consequences. While SUD treatment can be effective and diminish substance-related consequences, very few emerging adults with SUDs actually receive treatment and research is needed to identify potential determinants of receiving care. We examined associations between individual factors and social determinants of health (SDOH) with SUD treatment service utilization to inform treatment engagement strategies for emerging adults. Methods Using pooled cross-sectional data from the 2015–2019 years of the National Survey on Drug Use and Health, we evaluated past-year treatment utilization among emerging adults (i.e. respondents aged 18–25 years-old) with a past-year SUD (N = 12,594). Logistic regression analyses evaluated sex, race, education level, lifetime arrest history and age of alcohol initiation in addition to mental illness, employment, food stamp utilization, poverty status, and frequency of housing relocation. Results Past-year mental illness, Non-Hispanic White identity, not having a college degree, lifetime arrest history, part-time employment or unemployment, and relocating for housing more than 2 times in the past year were significantly associated with greater likelihood of treatment utilization in adjusted analyses. Conclusions Findings from this nationally representative survey of emerging adults highlight the possible contribution of some SDOH associated with social disadvantage and/or criminal justice involvement on SUD treatment utilization. These results may guide providers in tailoring service delivery mode, community organizations to target populations, and implementation strategies that are effective in reducing SUD treatment service utilization inequity.

Cocaine reward and reinstatement in adolescent versus adult rodents.

Adolescence is a critical juncture when initiation of drug use intersects with profound developmental changes in the brain. Adolescent drug use increases the risk to develop substance use disorders (SUDs) later in life, but the mechanisms that confer this vulnerability are not understood. SUDs are defined by cycles of use, abstinence, and relapse. Intense craving during drug-free periods is often triggered by cues and environmental contexts associated with previous use. In contrast to our understanding of stimuli that elicit craving and relapse in adults, the behavioral processes that occur during periods of abstinence and relapse in adolescents are poorly understood. The current mini-review will summarize findings from preclinical rodent studies that used cocaine conditioned place preference and operant cocaine self-administration to examine subsequent effects on reward, relapse and incubation of craving.

Bar press durations as a reliable and robust measure of frustration-related operant behavior: Sensitivity to incentive downshift and dose-response paradigms.

In humans, frustrating experiences are known to trigger relapse events and individuals with higher frustration intolerance show increased risk of developing substance use disorders (SUDs). Despite this clear relationship, frustration-related behavior is seldom studied concurrently with self-administration behavior in rodent models. A major obstacle has been the lack of robust, quantitative assays of frustration-related operant behavior thus far. In previous work, we identified increased bar press (BP) durations in response to frustrating conditions in rats self-administering natural or drug rewards. Here, to propose BP durations as a measure of frustration-related behavior, we conducted an operant successive negative contrast (oSNC) study and found that increases in BP durations are observed in the absence of increased effort, providing evidence that this is a psychological phenomenon. Moreover, we assess the viability of widespread use of BP duration measurements as a behavioral tool by quantifying performance as it pertains to sensitivity, robustness, replicability, and sex differences. We conclude that increases in BP durations are a highly sensitive psychological response to frustrating conditions and that this measure is robust, replicable, and applicable to both sexes.

Methadone dose escalation in patients with opioid use disorder and cancer as a strategy for controlling cancer-related pain: A case series.

Opioid use disorder (OUD) and cancer gained attention as co-occurring diseases in the last 2 decades due to the possible relationship between opioid prescriptions for cancer pain and the risk of developing substance use disorder in cancer patients. However, little is known about patients previously diagnosed with OUD who develop cancer and how to manage both OUD symptoms and control pain. The present case series deals with this subpopulation and proposes a dose escalation of methadone to control both the cancer-related pain and drug addiction symptoms. This approach is peculiar because methadone is not used as a first-line treatment in cancer pain management and is not often used as a second-line treatment as well. Our 4 patients experienced good clinical control of symptoms and no major adverse reactions. The subgroup of patients with OUD who develop cancer could be the perfect population to reconsider the use of methadone as a first-line treatment for cancer pain. Prospective studies are needed to evaluate the efficacy and safety of increasing doses of methadone in these patients to validate our clinical approach.

Building capacity to implement sexual health risk and substance use disorder prevention services in adolescent behavioral health treatment: A case study

Adolescents with mental health and psychiatric disorders, as compared to their peers, are at increased risk for contracting sexually transmitted infections and developing substance use disorders (SUD). Practitioners need integrated programs addressing sexual health and substance misuse to promote healthy behaviors among vulnerable adolescent populations. Building agency capacity necessary to integrate sexual health education and SUD prevention can be challenging, but dissemination and implementation frameworks and models can provide a structured approach. This case study examines the application of the Interactive Systems Framework for Dissemination and Implementation and the Evidence-based System for Innovation Support to build the capacity of behavioral health agency staff to deliver an integrated sexual health risk and SUD prevention program with adolescents. Over a five-year period, researchers and behavioral health agency staff collaborated and increased agency capacity by using a training-of-trainers approach, comprehensive tools, proactive technical assistance, and quality assurance. While there were significant challenges, such as staff turnover and competing agency priorities, the team certified eight facilitators in the selected health promotion intervention and two agency trainers with the capacity for ongoing expansion and the expectation of sustainability of needed adolescent services.

Sex, but not juvenile stress, affects reversal learning and DRL performance following cocaine administration

IntroductionEarly adversity, impulsivity and sex all contribute to the risk of developing substance use disorder. Using rats, we examined how juvenile stress interacts with sex and cocaine to affect performance on a serial reversal task and a differential reinforcement of low rates 10 s (DRL10) task. The expression of dopamine-related proteins in several brain areas was also assessed. MethodsFrom postnatal days (PND) 25–29, rats were exposed to a variable stress protocol. In adulthood, rats were trained on the reversal task and the effects of cocaine (0, 10, or 20 mg/kg, IP) on performance were assessed. Next, rats were trained on the DRL10 task and the effects of cocaine on performance were assessed. Finally, brains were extracted, and Western blot analyses conducted. ResultsJuvenile stress did not affect behavior. Sex did not affect baseline performance in either task. In the reversal task, cocaine decreased % high probability responses and the number of rewards earned in both sexes. Cocaine had sex-dependent effects on omissions, low probability responses and response latencies. In the DRL10 task, cocaine decreased the peak latency to respond and the number of rewards earned in both sexes. Cocaine had sex-dependent effects on peak rate of responding, response efficiency, burst responses and long responses. Female rats exhibited increased expression of DRD1 receptors in the striatum. DiscussionThese data contribute to the growing literature demonstrating sex differences in the behavioral effects of cocaine and suggest that DRD1 receptors could contribute to the observed behavioral sex differences.

Impact of early-life lead exposure on adult delta-9-tetrahydrocannabinol sensitivity in male and female C57BL6/J mice

Environmental exposure to lead (Pb) and cannabis use are two of the largest public health issues facing modern society in the United States and around the world. Exposure to Pb in early life has been unequivocally shown to have negative impacts on development, and recent research is mounting showing that it may also predispose individuals for risk of developing substance use disorders (SUD). At the same time, societal and legal attitudes towards cannabis (the main psychoactive component of which is delta-9-tetrahydrocannabinol) have been shifting, and many American states have legalized the recreational use of cannabis. It is also the 3rd most widely used drug of abuse in the US, and rates of cannabis use disorder are on the rise. Here we establish a link between early life Pb exposure and later THC-related behavior in C57BL6/J mice, as has been demonstrated for other drugs of abuse. The study seeks to answer whether Pb exposure affects physiological/behavioral THC sensitivity (as measured by the cannabinoid-induced tetrad). It was hypothesized that Pb exposure would decrease THC sensitivity and that sex-dependent effects of Pb-exposure and THC would be observed. Interestingly, results showed that THC sensitivity was increased by Pb exposure, but only in female mice. Future research will fully explore the implications of these findings, namely how these effects impact THC self-administration and the mechanism(s) by which developmental Pb exposure produces these effects.

Influence of reconsolidation in maintenance of cocaine-associated contextual memories formed during adolescence or adulthood

Adolescents are at increased risk to develop substance use disorders and suffer from relapse throughout life. Targeted weakening of drug-associated memories has been shown to reduce relapse-like behavior in adult rats, however this process has been understudied in adolescents. We aimed to examine whether adolescent-formed, cocaine-associated memories could be manipulated via reconsolidation mechanisms. To accomplish this objective, we used an abbreviated operant cocaine self-administration paradigm (ABRV Coc-SA). Adult and adolescent rats received jugular catheterization surgery followed by ABRV Coc-SA in a distinct context for 2 h, 2×/day over 5 days. Extinction training (EXT) occurred in a second context for 2 h, 2×/day over 4 days. To retrieve cocaine-context memories, rats were exposed to the cocaine-paired context for 15 min, followed by subcutaneous injection of vehicle or the protein synthesis inhibitor cycloheximide (2.5 mg/kg). Two additional EXT sessions were conducted before a 2 h reinstatement test in the cocaine-paired context to assess cocaine-seeking behavior. We find that both adult and adolescent cocaine-exposed rats show similar levels of cocaine-seeking behavior regardless of post-reactivation treatment. Our results suggest that systemic treatment with the protein synthesis inhibitor cycloheximide does not impair reconsolidation of cocaine-context memories and subsequent relapse during adulthood or adolescence.

MAOA uVNTR Polymorphism Influence on Older Adults Diagnosed with Diabetes Mellitus/Systemic Arterial Hypertension.

Monoamine oxidase (MAO) is involved in several biological processes associated with well-being and mental health, and alterations in its function might directly impact various mental disorders. Some mental disorders concomitantly occur in individuals with clinical characteristics, such as substance abuse and diabetes. To analyze the functional MAOA uVNTR polymorphism genotype frequency in an older adult population with diabetes mellitus/arterial hypertension and associate this frequency with clinical characteristics impacting daily life. Methodology. Older adults diagnosed with diabetes mellitus, systemic arterial hypertension, or both (DM/SAH) were selected and had their MAOA gene genotyped for uVNTR polymorphism. The revised Beck Depression Inventory (BDI) and a questionnaire were also applied to determine their mental health and clinical characteristics. The allelic variants detected among the participants were the 2R, 3R, 4R, and 3R/4R heterozygous genotypes. Genotypes solely containing the 3R allele had patients who marked yes for smoking and alcoholism, and only those with the 3R genotypes (female 3R/3R homozygote or male 3R∗ hemizygote) were significant. Although not statistically significant, only 3R and 3R/4R genotypes presented cases of severe depression per the revised BDI interpretations. The MAOA uVNTR polymorphism's low-activity 3R allele presence in an older adult population diagnosed with DM/SAH may represent a risk for developing substance use (alcohol and smoking) dependence.

Patterns and perceptions of nicotine use among U.S. adolescents and young adults receiving medication treatment for opioid use disorder

Nicotine use among U.S. youth is cause for concern, as previous studies have shown that nicotine use in adolescence increases the risk of developing substance use disorders later in life. This exploratory study aimed to understand patterns of nicotine use and perceptions of various nicotine products among adolescents and young adults (AYA) receiving medication treatment for opioid use disorder (MOUD). We administered an adapted version of the National Youth Tobacco Survey via REDCap to AYA (n = 32) receiving outpatient care in the Medication-Assisted Treatment of Addiction at Nationwide Children’s Hospital in Columbus, Ohio, U.S.A. Thirty (97%) participants had tried a combustible cigarette and 27 (90%) had tried an electronic cigarette. By age 13, nineteen (61%) participants had tried combustible cigarettes and eight (25%) had tried opioids. Twenty-two (71%) participants reported smoking combustible cigarettes every day for the past 30 days, and 15 (48%) reported smoking more than 10 cigarettes per day on average. Only ten (32%) participants reported e-cigarette use in the last 30 days. Participants universally agreed that tobacco products are dangerous, and twenty (67%) current tobacco users reported that they planned to quit in the next year. Nicotine use patterns among AYA receiving MOUD differ from that previously shown in the general population, primarily by high prevalence of nicotine use in early adolescence and high current combustible cigarette use. Interventions such as universal screening for nicotine use before age 13 and tailored smoking cessation programs for AYA with OUD may help optimize care for these individuals.