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1.
PLoS One ; 19(6): e0304219, 2024.
Article in English | MEDLINE | ID: mdl-38843195

ABSTRACT

INTRODUCTION: Illicit drug use is a significant public health problem. Studies have shown a high prevalence of cocaine and cannabis use in transgender women (TGW). OBJECTIVE: To describe the consumption patterns of cannabis and cocaine/crack use and variables associated with their use in TGW in Central Brazil. METHODS: A cross-sectional study was conducted on TGW in Goiás, Brazil. Participants were recruited using a respondent-driven sampling method and were interviewed face-to-face about cannabis and crack-cocaine and the variables associated with them. The Alcohol Smoking and Substance Involvement Screening Test was used to assess substance use. Unweighted logistic regression was used to identify variables associated with cannabis and crack cocaine use. P-values < 0.05 were considered statistically significant. RESULTS: A total of 440 transgender women participated in the study. Their median age was 25 years (interquartile range: 20.5-29.5 years). Most participants were single (85.5%) and had engaged in sex work in their lifetime (58.6%). Cannabis was reported by 68.9% and 53.4% of participants in their lifetime and in the past three months, respectively, and cocaine/crack use was reported by 59.8% and 44.1% of participants in their lifetime and the past three months, respectively. Of the participants, 10.2% reported high-risk cannabis use, and 9.1% reported high-risk cocaine/crack use. Furthermore, 35% of participants reported using both drugs. Previous physical violence (Adjusted Odds Ratio (AOR): 2.37), inconsistent condom uses during anal sex (AOR: 2.17), and moderate-/high-risk cocaine/crack use (AOR: 3.14) were associated with high-risk cannabis use. Previous sexual violence (AOR: 2.84), previous STI (AOR: 2.90), moderate-/high-risk cannabis (AOR: 3.82), and binge drinking (AOR; 3.28) were associated with high-risk cocaine/crack use. CONCLUSION: Our study found a high frequency, significant overlap in the use of cannabis and cocaine/crack use and violence associated with these drugs consumption among TGW, highlighting the urgent need for health policies for drug disorders among this socially marginalized group.


Subject(s)
Crack Cocaine , Transgender Persons , Humans , Female , Brazil/epidemiology , Adult , Transgender Persons/statistics & numerical data , Cross-Sectional Studies , Young Adult , Cocaine-Related Disorders/epidemiology , Prevalence , Male , Marijuana Abuse/epidemiology , Cannabis/adverse effects
2.
Syst Rev ; 13(1): 124, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720357

ABSTRACT

BACKGROUND: Psychosocial approaches are the first-line treatments for cocaine dependence, although they still present high dropout and relapse rates. Thus, there is a pressing need to understand which variables influence treatment outcomes to improve current treatments and prevent dropout and relapse rates. The aim of this study is to explore predictors of treatment retention and abstinence in CUD. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched three databases-PubMed, PsychINFO and Web of Science-for randomized clinical trials (RCTs) published in English and Spanish from database inception through April 1, 2023. We selected all studies that met the inclusion criteria (adults aged ≥ 18, outpatient treatment, CUD as main addiction, and no severe mental illness) to obtain data for the narrative synthesis addressing cocaine abstinence and treatment retention as main outcome variables. After data extraction was completed, risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB-2). RESULTS: A total of 566 studies were screened, and, of those, 32 RCTs were included in the synthesis. Younger age, more years of cocaine use, and craving levels were significant predictors of relapse and treatment dropout. Fewer withdrawal symptoms, greater baseline abstinence, greater treatment engagement, and more self-efficacy were all predictors of longer duration of abstinence. The role of impulsivity as a predictor of CUD is unclear due to conflicting data, although the evidence generally suggests that higher impulsivity scores can predict more severe addiction and withdrawal symptoms, and earlier discontinuation of treatment. CONCLUSION: Current evidence indicates which variables have a direct influence on treatment outcomes, including well-studied cocaine use-related variables. However, additional variables, such as genetic markers, appear to have a high impact on treatment outcomes and need further study. SYSTEMATIC REVIEW REGISTRATION: This systematic review is registered at PROSPERO (ID: CRD42021271847). This study was funded by the Spanish Ministry of Science, Innovation and Universities, Instituto Carlos III (ISCIII) (FIS PI20/00929) and FEDER funds and Fundació Privada Hospital de la Santa Creu i Sant Pau (Pla d'acció social 2020).


Subject(s)
Cocaine-Related Disorders , Humans , Cocaine-Related Disorders/therapy , Cocaine-Related Disorders/psychology , Treatment Outcome , Recurrence , Craving , Self Efficacy , Patient Dropouts/statistics & numerical data , Randomized Controlled Trials as Topic , Age Factors , Substance Withdrawal Syndrome
4.
Addict Biol ; 29(5): e13397, 2024 May.
Article in English | MEDLINE | ID: mdl-38711205

ABSTRACT

Neuronal ensembles in the medial prefrontal cortex mediate cocaine self-administration via projections to the nucleus accumbens. We have recently shown that neuronal ensembles in the prelimbic cortex form rapidly to mediate cocaine self-administration. However, the role of neuronal ensembles within the nucleus accumbens in initial cocaine-seeking behaviour remains unknown. Here, we sought to expand the current literature by testing the necessity of the cocaine self-administration ensemble in the nucleus accumbens core (NAcCore) 1 day after male and female rats acquire cocaine self-administration by using the Daun02 inactivation procedure. We found that disrupting the NAcCore ensembles after a no-cocaine reward-seeking test increased subsequent cocaine seeking, while disrupting NAcCore ensembles following a cocaine self-administration session decreased subsequent cocaine seeking. We then characterized neuronal cell type in the NAcCore using RNAscope in situ hybridization. In the no-cocaine session, we saw reduced dopamine D1 type neuronal activation, while in the cocaine self-administration session, we found preferential dopamine D1 type neuronal activity in the NAcCore.


Subject(s)
Cocaine , Drug-Seeking Behavior , Neurons , Nucleus Accumbens , Self Administration , Animals , Nucleus Accumbens/drug effects , Cocaine/pharmacology , Male , Female , Rats , Drug-Seeking Behavior/drug effects , Neurons/drug effects , Reward , Dopamine Uptake Inhibitors/pharmacology , Reinforcement, Psychology , Receptors, Dopamine D1 , Cocaine-Related Disorders/physiopathology , Rats, Sprague-Dawley , Prefrontal Cortex/drug effects
5.
An Acad Bras Cienc ; 96(2): e20240014, 2024.
Article in English | MEDLINE | ID: mdl-38747842

ABSTRACT

Despite the prevalence of substance use during pregnancy, studies focusing exclusively on Neonatal Intensive Care Units (NICU) admissions remain limited. This study investigates the impact of maternal use of tobacco, alcohol, and/or crack, on neonatal outcomes among infants admitted to three Brazilian NICUs. Additionally, the investigation explores the impact of substance use on DNA damage in newborns. Over a one-year period, data from 254 newborns were collected through medical records, accompanied by blood samples. Findings revealed that 16.1% of newborns had mothers reporting substance use during pregnancy. Significant associations were found between maternal substance use and adverse neonatal outcomes, including low birth weight, preterm birth, and sexually transmitted infections. Maternal variables linked to substance use encompassed non-white skin color, low education, non-masonry housing, lower income, diseases in other children, and fewer prenatal consultations. Notably, neonatal DNA damage showed no significant association with substance use. Our results underscore the substantial impact of maternal substance use on NICU-admitted infants, emphasizing the necessity for targeted interventions that address both neonatal health and maternal well-being, thereby underscoring the crucial role of comprehensive care in NICU settings.


Subject(s)
Alcohol Drinking , Intensive Care Units, Neonatal , Humans , Pregnancy , Female , Infant, Newborn , Brazil/epidemiology , Adult , Alcohol Drinking/adverse effects , Pregnancy Complications , Male , Young Adult , Pregnancy Outcome , Infant, Low Birth Weight , Crack Cocaine/adverse effects , Cocaine-Related Disorders/epidemiology , Risk Factors , Socioeconomic Factors , DNA Damage , Prenatal Exposure Delayed Effects
6.
Transl Psychiatry ; 14(1): 214, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802366

ABSTRACT

Relapse to drug use after abstinence is a major challenge in treating substance use disorder. Exposure to drug-associated cues during abstinence can trigger intense craving and precipitate relapse. New and more effective anti-relapse interventions are critically needed, particularly for cocaine use disorder since no effective pharmacological intervention is available. We discovered that a nutritional supplement we developed as part of a nutritional approach for managing patients with substance use disorder reduced patient reports of drug craving and relapse. The goal of this study was to determine the efficacy of this supplement, SMAASH-C, at reducing drug-craving/relapse vulnerability in males and females in rat models with cocaine. Effects were determined following extended-access cocaine self-administration (24-hr/day for 10 days) and a two-week treatment regimen at a moderate and moderate-to-high dose (0.4 and 0.8 g/kg/day) as well as a 6-week regimen at a moderate dose (0.4 g/kg/day; Experiment 2). We also determined its efficacy to offset serum markers of organ toxicity in response to chronic cocaine self-administration and abstinence (aspartate transaminase, alanine transaminase, amylase; urea nitrogen). In females, both the 2- and 6-week SMAASH-C treatment regimens reduced cocaine-seeking (extinction or cue-induced reinstatement), particularly when drug-seeking was heightened (e.g., during estrus). Despite a lack of efficacy to reduce drug-seeking in males, SMAASH-C treatment normalized cocaine/abstinence-induced increases in serum levels of aspartate transaminase and amylase, which are markers of liver and pancreatic toxicity respectively. Thus, the beneficial effects of oral SMAASH-C treatment over abstinence following chronic cocaine self-administration appears to be sex-specific.


Subject(s)
Cocaine-Related Disorders , Cocaine , Dietary Supplements , Drug-Seeking Behavior , Self Administration , Animals , Male , Female , Rats , Drug-Seeking Behavior/drug effects , Cocaine/administration & dosage , Craving/drug effects , Rats, Sprague-Dawley , Cues , Disease Models, Animal
9.
Methodist Debakey Cardiovasc J ; 20(1): 26-32, 2024.
Article in English | MEDLINE | ID: mdl-38799179

ABSTRACT

We present the case of a 60-year-old male, with active smoking and cocaine use disorder, who reported progressive chest pain. Various anatomical and functional cardiac imaging, performed to further evaluate chest pain etiology, revealed changing severity and distribution of left main artery (LMA) stenosis, raising suspicion for vasospasm. Intracoronary nitroglycerin relieved the vasospasm, with resolution of the LMA pseudostenosis. A diagnosis of vasospastic angina (VA) led to starting appropriate medical therapy with lifestyle modification counselling. This case highlights VA, a frequently underdiagnosed etiology of angina pectoris. We discuss when to suspect VA, its appropriate work-up, and management.


Subject(s)
Coronary Angiography , Coronary Stenosis , Coronary Vasospasm , Nitroglycerin , Vasodilator Agents , Humans , Male , Middle Aged , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/therapy , Coronary Stenosis/physiopathology , Coronary Vasospasm/diagnostic imaging , Coronary Vasospasm/physiopathology , Coronary Vasospasm/drug therapy , Coronary Vasospasm/therapy , Coronary Vasospasm/diagnosis , Nitroglycerin/administration & dosage , Treatment Outcome , Vasodilator Agents/therapeutic use , Vasodilator Agents/administration & dosage , Predictive Value of Tests , Cocaine-Related Disorders/complications , Severity of Illness Index , Angina Pectoris/etiology , Angina Pectoris/diagnostic imaging , Diagnosis, Differential , Smoking/adverse effects
10.
J Int Med Res ; 52(4): 3000605241237876, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38606757

ABSTRACT

Differentiation between granulomatosis with polyangiitis (GPA) limited to the upper airways and cocaine-induced midline destructive lesion (CIMDL) may be particularly difficult because of their common histopathologic features and antineutrophil cytoplasmic antibody (ANCA) profiles. We herein present a case involving a young woman with an initial diagnosis of GPA based on upper and lower airway manifestations and constitutional symptoms, histopathologic evidence of granulomas, a positive cytoplasmic ANCA indirect immunofluorescent test result, and proteinase 3 positivity by enzyme-linked immunosorbent assay (ELISA). CIMDL was confirmed based on the appearance of a hard palate perforation, positivity for methylecgonine on urine toxicology, a positive perinuclear ANCA indirect immunofluorescent test result, and subsequent human neutrophil elastase (HNE) ANCA positivity by ELISA. Finally, based on the coexistence of CIMDL, constitutional symptoms, and lower airway manifestations, the diagnosis was modified to cocaine-induced GPA mimic. Urine toxicology for cocaine and HNE ELISA are indicated in young patients with GPA who develop limited airway disease to check for the presence of CIMDL and cocaine-/levamisole-induced ANCA-associated vasculitis. Continued abstinence from cocaine is the first-choice therapy for both CIMDL and cocaine-induced GPA mimic.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Cocaine-Related Disorders , Cocaine , Granulomatosis with Polyangiitis , Female , Humans , Antibodies, Antineutrophil Cytoplasmic , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/complications , Cocaine-Related Disorders/complications , Cocaine-Related Disorders/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications
11.
Dev Psychobiol ; 66(4): e22493, 2024 May.
Article in English | MEDLINE | ID: mdl-38643355

ABSTRACT

Prenatal drug exposure is a public health problem, which results in profound behavioral problems during childhood and adolescence, mainly represented by an increase in the risk of cocaine abuse at an early age. In rodents, prenatal and postnatal cocaine exposure enhanced locomotor activity and cocaine- or nicotine-induced locomotor sensitization. Various authors consider that the adverse emotional states (anxiety and depression) that occur during cocaine withdrawal are the main factors that precipitate, relapse, and increase chronic cocaine abuse, which could increase the risk of relapse of cocaine abuse. Therefore, the objective of this study was to characterize anxiety- and depression-like behaviors at different times (30, 60, 90, and 120 days) of cocaine withdrawal in rats born to females exposed prenatally and postnatally to cocaine. A group of pregnant female Wistar rats were administered daily from day GD0 to GD21 with cocaine (cocaine preexposure group), and another group of pregnant female rats was administered daily with saline (saline preexposure group). Of the litters resulting from the cocaine-pre-exposed and saline-pre-exposed pregnant female groups, only the male rats were used for the recording of the anxiety- and depression-like behaviors at different times (30, 60, 90, and 120 days) of cocaine withdrawal The study found that prenatal and postnatal cocaine exposure dose-dependent enhanced anxiety- and depression-like behaviors. This suggests that prenatal and postnatal cocaine exposure can result in enhanced vulnerability to cocaine abuse in young and adult humans.


Subject(s)
Cocaine-Related Disorders , Cocaine , Substance Withdrawal Syndrome , Humans , Pregnancy , Adolescent , Adult , Rats , Animals , Male , Female , Cocaine/adverse effects , Depression/psychology , Rats, Sprague-Dawley , Rats, Wistar , Behavior, Animal , Anxiety/psychology , Recurrence
12.
Sci Data ; 11(1): 408, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649689

ABSTRACT

Cocaine use disorder (CUD) is a global health problem with severe consequences, leading to behavioral, cognitive, and neurobiological disturbances. While consensus on treatments is still ongoing, repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising approach for medication-resistant disorders, including substance use disorders. In this context, here we present the SUDMEX-TMS, a Mexican dataset from an rTMS clinical trial involving CUD patients. This longitudinal dataset comprises 54 CUD patients (including 8 females) with data collected at five time points: baseline (T0), two weeks (T1), three months (T2), six months (T3) follow-up, and twelve months (T4) follow-up. The clinical rTMS treatment followed a double-blinded randomized clinical trial design (n = 24 sham/30 active) for 2 weeks, followed by an open-label phase. The dataset includes demographic, clinical, and cognitive measures, as well as magnetic resonance imaging (MRI) data collected at all time points, encompassing structural (T1-weighted), functional (resting-state fMRI), and multishell diffusion-weighted (DWI-HARDI) sequences. This dataset offers the opportunity to investigate the impact of rTMS on CUD participants, considering clinical, cognitive, and multimodal MRI metrics in a longitudinal framework.


Subject(s)
Cocaine-Related Disorders , Transcranial Magnetic Stimulation , Adult , Female , Humans , Male , Cocaine-Related Disorders/therapy , Longitudinal Studies , Magnetic Resonance Imaging , Mexico , Randomized Controlled Trials as Topic
13.
Addict Behav ; 155: 108027, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38581751

ABSTRACT

Cue reactivity is relevant across addictive disorders as a process relevant to maintenance, relapse, and craving. Understanding the neurobiological foundations of cue reactivity across substance and behavioral addictions has important implications for intervention development. The present study used intrinsic connectivity distribution methods to examine functional connectivity during a cue-exposure fMRI task involving gambling, cocaine and sad videos in 22 subjects with gambling disorder, 24 with cocaine use disorder, and 40 healthy comparison subjects. Intrinsic connectivity distribution implicated the posterior cingulate cortex (PCC) at a stringent whole-brain threshold. Post-hoc analyses investigating the nature of the findings indicated that individuals with gambling disorder and cocaine use disorder exhibited decreased connectivity in the posterior cingulate during gambling and cocaine cues, respectively, as compared to other cues and compared to other groups. Brain-related cue reactivity in substance and behavioral addictions involve PCC connectivity in a content-to-disorder specific fashion. The findings suggesting that PCC-related circuitry underlies cue reactivity across substance and behavioral addictions suggests a potential biomarker for targeting in intervention development.


Subject(s)
Cocaine-Related Disorders , Cues , Gambling , Gyrus Cinguli , Magnetic Resonance Imaging , Humans , Cocaine-Related Disorders/physiopathology , Cocaine-Related Disorders/psychology , Gyrus Cinguli/physiopathology , Gyrus Cinguli/diagnostic imaging , Male , Gambling/physiopathology , Gambling/psychology , Adult , Female , Case-Control Studies , Middle Aged , Young Adult , Craving/physiology , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging
14.
Behav Pharmacol ; 35(4): 147-155, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38651979

ABSTRACT

Previous exposure to drugs of abuse produces impairments in studies of reversal learning, delay discounting and response inhibition tasks. While these studies contribute to the understanding of normal decision-making and how it is impaired by drugs of abuse, they do not fully capture how decision-making impacts the ability to delay gratification for greater long-term benefit. To address this issue, we used a diminishing returns task to study decision-making in rats that had previously self-administered cocaine. This task was designed to test the ability of the rat to choose to delay gratification in the short-term to obtain more reward over the course of the entire behavioral session. Rats were presented with two choices. One choice had a fixed amount of time delay needed to obtain reward [i.e. fixed delay (FD)], while the other choice had a progressive delay (PD) that started at 0 s and progressively increased by 1 s each time the PD option was selected. During the 'reset' variation of the task, rats could choose the FD option to reset the time delay associated with the PD option. Consistent with previous results, we found that prior cocaine exposure reduced rats' overall preference for the PD option in post-task reversal testing during 'no-reset' sessions, suggesting that cocaine exposure made rats more sensitive to the increasing delay of the PD option. Surprisingly, however, we found that rats that had self-administered cocaine 1-month prior, adapted behavior during 'reset' sessions by delaying gratification to obtain more reward in the long run similar to control rats.


Subject(s)
Cocaine , Delay Discounting , Reward , Self Administration , Animals , Cocaine/pharmacology , Cocaine/administration & dosage , Male , Delay Discounting/drug effects , Rats , Choice Behavior/drug effects , Conditioning, Operant/drug effects , Dopamine Uptake Inhibitors/pharmacology , Dopamine Uptake Inhibitors/administration & dosage , Decision Making/drug effects , Cocaine-Related Disorders/psychology , Rats, Long-Evans , Time Factors
15.
Sci Signal ; 17(832): eadl4738, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38626009

ABSTRACT

Cocaine use disorder (CUD) is a chronic neuropsychiatric condition that results from enduring cellular and molecular adaptations. Among substance use disorders, CUD is notable for its rising prevalence and the lack of approved pharmacotherapies. The nucleus accumbens (NAc), a region that is integral to the brain's reward circuitry, plays a crucial role in the initiation and continuation of maladaptive behaviors that are intrinsic to CUD. Leveraging advancements in neuroproteomics, we undertook a proteomic analysis that spanned membrane, cytosolic, nuclear, and chromatin compartments of the NAc in a mouse model. The results unveiled immediate and sustained proteomic modifications after cocaine exposure and during prolonged withdrawal. We identified congruent protein regulatory patterns during initial cocaine exposure and reexposure after withdrawal, which contrasted with distinct patterns during withdrawal. Pronounced proteomic shifts within the membrane compartment indicated adaptive and long-lasting molecular responses prompted by cocaine withdrawal. In addition, we identified potential protein translocation events between soluble-nuclear and chromatin-bound compartments, thus providing insight into intracellular protein dynamics after cocaine exposure. Together, our findings illuminate the intricate proteomic landscape that is altered in the NAc by cocaine use and provide a dataset for future research toward potential therapeutics.


Subject(s)
Cocaine-Related Disorders , Cocaine , Mice , Animals , Nucleus Accumbens/metabolism , Proteomics , Cocaine/pharmacology , Cocaine-Related Disorders/genetics , Cocaine-Related Disorders/metabolism , Cocaine-Related Disorders/psychology , Chromatin/metabolism
16.
Drug Alcohol Depend ; 259: 111288, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38648721

ABSTRACT

BACKGROUND: Cocaine consumption is associated with reduced attentional event-related potentials (ERPs), namely P3a and P3b, indicating bottom-up and top-down deficits respectively. At cognitive level, these impairments are larger for faster routes of administration (e.g., smoked cocaine [SC]) than slower routes (e.g., insufflated cocaine [IC]). Here we assess these ERPs considering the route of cocaine administration. We hypothesized that SC dependent (SCD) would exhibit reduced amplitude of the P3a, while both SCD and IC dependent (ICD) would show reduced amplitude of the P3b. METHODS: We examined 25 SCD, 22 ICD matched by poly-consumption profiles, and 25 controls matched by demographic variables. We combined EEG data from the Global-Local task with behavioral data from attentional cognitive tasks. RESULTS: At the behavioral level, SCD exhibited attentional deficits in both bottom-up and top-down processes, while ICD only showed a tendency for top-down deficits. The amplitude of P3a and P3b was lower in Users groups. We observed subtle route-based differences, with larger differences in the P3a for SCD and in the P3b for ICD. Neurophysiological and behavioral data converged, with the P3a associated to bottom-up performance and P3b to top-down. CONCLUSIONS: Different routes of administration lead to distinct attentional neurocognitive profiles. Specifically, SCD showed greater attentional impairment, mainly at bottom-up/P3a, while ICD showed a trend of top-down/P3b deficits. These findings emphasize the crucial role of considering the route of administration in both clinical and research settings and support the use of attentional ERPs as valid measures for assessing attentional deficits in substance Dependence.


Subject(s)
Attention , Cocaine-Related Disorders , Electroencephalography , Evoked Potentials , Neuropsychological Tests , Humans , Male , Adult , Female , Attention/drug effects , Attention/physiology , Cocaine-Related Disorders/psychology , Cocaine-Related Disorders/physiopathology , Evoked Potentials/physiology , Evoked Potentials/drug effects , Cocaine/administration & dosage , Event-Related Potentials, P300/physiology , Event-Related Potentials, P300/drug effects , Young Adult , Middle Aged
17.
J Neurosci ; 44(23)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38637154

ABSTRACT

Cocaine use disorder is a significant public health issue without an effective pharmacological treatment. Successful treatments are hindered in part by an incomplete understanding of the molecular mechanisms that underlie long-lasting maladaptive plasticity and addiction-like behaviors. Here, we leverage a large RNA sequencing dataset to generate gene coexpression networks across six interconnected regions of the brain's reward circuitry from mice that underwent saline or cocaine self-administration. We identify phosphodiesterase 1b (Pde1b), a Ca2+/calmodulin-dependent enzyme that increases cAMP and cGMP hydrolysis, as a central hub gene within a nucleus accumbens (NAc) gene module that was bioinformatically associated with addiction-like behavior. Chronic cocaine exposure increases Pde1b expression in NAc D2 medium spiny neurons (MSNs) in male but not female mice. Viral-mediated Pde1b overexpression in NAc reduces cocaine self-administration in female rats but increases seeking in both sexes. In female mice, overexpressing Pde1b in D1 MSNs attenuates the locomotor response to cocaine, with the opposite effect in D2 MSNs. Overexpressing Pde1b in D1/D2 MSNs had no effect on the locomotor response to cocaine in male mice. At the electrophysiological level, Pde1b overexpression reduces sEPSC frequency in D1 MSNs and regulates the excitability of NAc MSNs. Lastly, Pde1b overexpression significantly reduced the number of differentially expressed genes (DEGs) in NAc following chronic cocaine, with discordant effects on gene transcription between sexes. Together, we identify novel gene modules across the brain's reward circuitry associated with addiction-like behavior and explore the role of Pde1b in regulating the molecular, cellular, and behavioral responses to cocaine.


Subject(s)
Cocaine-Related Disorders , Cyclic Nucleotide Phosphodiesterases, Type 1 , Gene Regulatory Networks , Mice, Inbred C57BL , Nucleus Accumbens , Sex Characteristics , Animals , Male , Female , Cyclic Nucleotide Phosphodiesterases, Type 1/genetics , Cyclic Nucleotide Phosphodiesterases, Type 1/metabolism , Mice , Cocaine-Related Disorders/genetics , Cocaine-Related Disorders/metabolism , Gene Regulatory Networks/drug effects , Gene Regulatory Networks/genetics , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Rats , Cocaine/pharmacology , Reward
18.
Article in English | MEDLINE | ID: mdl-38649130

ABSTRACT

Cocaine use disorder (CUD) is a global health problem with no approved medications. One potential treatment target is the gut microbiome, but it is unknown if cocaine induces long-lasting effects on gut microbes. A novel therapeutic candidate for CUD, cannabidiol (CBD), can improve gut function in rodent models. It is possible that protective effects of CBD against cocaine use are mediated by improving gut health. We examined this question in this experiment. Cocaine conditioned place preference (CPP) was conducted in adult male C57BL/6JArc mice. Mice were treated with vehicle or 20 mg/kg CBD prior to all cocaine CPP sessions (N = 11-13/group). Mice were tested drug free 1, 14 and 28 days after cessation of cocaine and CBD treatment. Fecal samples were collected prior to drug treatment and after each test session. Gut microbiome analyses were conducted using 16 s rRNA sequencing and correlated with behavioural parameters. We found a persistent preference for a cocaine-environment in mice, and long-lasting changes to gut microbe alpha diversity. Cocaine caused persistent changes to beta diversity which lasted for 4 weeks. CBD treatment reduced cocaine-environment preference during abstinence from cocaine and returned gut beta diversity measures to control levels. CBD treatment increased the relative abundance of Firmicutes phyla and Oscillospira genus, but decreased Bacteroidetes phyla and Bacteroides acidifaciens species. Preference score in cocaine-treated mice was positively correlated with abundance of Actinobacteria, whereas in mice treated with CBD and cocaine, the preference score was negatively correlated with Tenericutes abundance. Here we show that CBD facilitates cocaine extinction memory and reverses persistent cocaine-induced changes to gut microbe diversity. Furthermore, CBD increases the abundance of gut microbes which have anti-inflammatory properties. This suggests that CBD may act via the gut to reduce the memory of cocaine reward. Our data suggest that improving gut health and using CBD could limit cocaine abuse.


Subject(s)
Cannabidiol , Cocaine , Extinction, Psychological , Gastrointestinal Microbiome , Mice, Inbred C57BL , Animals , Cannabidiol/pharmacology , Male , Gastrointestinal Microbiome/drug effects , Cocaine/pharmacology , Mice , Extinction, Psychological/drug effects , Cocaine-Related Disorders/drug therapy
19.
Rev. Ciênc. Plur ; 10 (1) 2024;10(1): 32867, 2024 abr. 30. tab
Article in Portuguese | LILACS, BBO - Dentistry | ID: biblio-1553542

ABSTRACT

Introdução: A utilização de cocaína é bastante associada ao surgimento de algumas manifestações sistêmicas e também de algumas alterações orais. Objetivo: Identificaras alterações sistêmicas e bucais mais comuns a pacientes usuários de cocaína. Metodologia: Trata-se de uma revisão sistemática da literatura, considerando artigos com texto completo, com restrição de idioma em Português ou Inglês e que tenham sido publicados entre os anos de 2017 a 2022. Usou-se as bases de dados LiLaCS, MedLine e BBO, por via portal Biblioteca Virtual de Saúde, e SciELO. Os artigos excluídosf oram aqueles que não apresentaram relação explícita do uso de cocaína com alguma manifestação sistêmica e/ou bucal. Resultados: Após o processo de triagem,10 artigos foram salvos para serem analisados e 111 foram descartados por não atenderem aos critérios de inclusão. Dos 10 artigosselecionados,40% deles (n=4) trouxeram informações identificando possíveis riscos de desenvolvimento de doenças cardiovasculares sofridas pelos usuários de cocaína, 10%(n=1) identificou problemas cognitivos associados ao uso da cocaína,30% dos artigos (n=3) mostrou as alterações bucais associadas à utilização abusiva de cocaína. Conclusões: Houve a predominância de algumas manifestações sistêmicas e bucais nos indivíduos usuários de cocaína, como doenças cardiovasculares, xerostomia, perfurações no palato, etc. A partir disso, há algumas alterações sistêmicas e bucais provocadas por esse uso. Mediante o risco considerável, faz-se necessário que o Cirurgião-Dentista se atualize sobre essas alterações em pacientes usuários de cocaína visando promover um trabalho transdisciplinare multiprofissional para atender adequadamente às suas necessidades (AU).


Introduction: The use of cocaine is closely associated with the appearance of some systemic manifestations and also some oral alterations.Objective: To identify the most common systemic and oral alterations in cocaine-using patients.Methodology:This is a systematic review of the literature, considering full-text articles, with a language restriction of "Portuguese" or "English" and published between 2017 and 2022. We used the LiLaCS, MedLine and BBO databases, via the Virtual Health Library (VHL) portal, and SciELO.The articles excluded were those that did not explicitly relate cocaine use to some systemic and/or oral manifestation.Results: After the screening process, 10 articles were saved for analysis and 111 were discarded because they did not meet the inclusion criteria. Of the 10 articles selected, 40% (n=4) provided information identifying possible risks of developing cardiovascular diseases suffered by cocaine users, 10% (n=1)identified cognitive problems associated with cocaine use, 30% of the articles (n=3) showed oral alterations associated with cocaine abuse.Conclusions: There has been a predominance of some systemic and oral manifestations in cocaine users, such as cardiovascular diseases, xerostomia, perforations in the palate, etc. Based on this, there are some systemic and oral alterations caused by this use. Given the considerable risk, it is necessary for dentists to be up-to-date on these alterations in cocaine-using patients in order to promote transdisciplinary and multi-professional work to adequately meet their needs (AU).


Introducción: El consumo de cocaína está estrechamente asociado a la aparición de algunas manifestaciones sistémicas y también de algunas alteraciones orales. Objetivo:Identificar las alteraciones sistémicas y bucales más frecuentes en los consumidores de cocaína. Metodología: Se trata de una revisión sistemática de la literatura, considerando artículos a texto completo, con restricción de idioma en "portugués" o "inglés" y publicados entre 2017 y 2022. Se utilizaron las bases de datos LiLaCS, MedLine y BBO, a través del portal Biblioteca Virtual en Salud (BVS) y SciELO. Los artículos excluidos fueron aquellos que no mostraban una relación explícita entre el consumo de cocaína y alguna manifestación sistémica y/o oral. Resultados: Tras el proceso de cribado, se guardaron10 artículos para el análisis y se descartaron 111 por no cumplir los criterios de inclusión. De los 10 artículos seleccionados, el 40% (n=4) proporcionaba información que identificaba posibles riesgos de desarrollar enfermedades cardiovasculares sufridaspor consumidores de cocaína, el 10% (n=1) identificaba problemas cognitivos asociados al consumo de cocaína, el 30% de los artículos (n=3) mostraban alteraciones orales asociadas al abuso de cocaína.Conclusiones:Ha habido un predominio de algunas manifestaciones sistémicas y orales en los consumidores de cocaína, como enfermedades cardiovasculares, xerostomía, perforaciones en el paladar, etc. De acuerdo con esto, existen algunas alteraciones sistémicas y orales causadas por este uso. Dado el considerable riesgo, es necesario que los odontólogos estén al día sobre estas alteraciones en los pacientes consumidores de cocaína, con el fin de promover el trabajo transdisciplinar y multiprofesional para atender adecuadamente sus necesidades (AU).


Subject(s)
Humans , Cocaine/pharmacology , Cocaine-Related Disorders , Dentists , Drug Users , Substance-Related Disorders , Health Services Needs and Demand
20.
J Neurosci ; 44(17)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38514181

ABSTRACT

The initiation of abstinence after chronic drug self-administration is stressful. Cocaine-seeking behavior on the first day of the absence of the expected drug (Extinction Day 1, ED1) is reduced by blocking 5-HT signaling in dorsal hippocampal cornu ammonis 1 (CA1) in both male and female rats. We hypothesized that the experience of ED1 can substantially influence later relapse behavior and that dorsal raphe (DR) serotonin (5-HT) input to CA1 may be involved. We inhibited 5-HT1A/1B receptors (WAY-100635 plus GR-127935), or DR input (chemogenetics), in CA1 on ED1 to test the role of this pathway on cocaine-seeking persistence 2 weeks later. We also inhibited 5-HT1A or 5-HT1B receptors in CA1 during conditioned place preference (CPP) for cocaine, to examine mechanisms involved in the persistent effects of ED1 manipulations. Inhibition of DR inputs, or 5-HT1A/1B signaling, in CA1 decreased drug seeking on ED1 and decreased cocaine seeking 2 weeks later revealing that 5-HT signaling in CA1 during ED1 contributes to persistent drug seeking during abstinence. In addition, 5-HT1B antagonism alone transiently decreased drug-associated memory performance when given prior to a CPP test, whereas similar antagonism of 5-HT1A alone had no such effect but blocked CPP retrieval on a test 24 h later. These CPP findings are consistent with prior work showing that DR inputs to CA1 augment recall of the drug-associated context and drug seeking via 5-HT1B receptors and prevent consolidation of the updated nondrug context via 5-HT1A receptors. Thus, treatments that modulate 5-HT-dependent memory mechanisms in CA1 during initial abstinence may facilitate later maintenance of abstinence.


Subject(s)
Cocaine , Drug-Seeking Behavior , Oxadiazoles , Serotonin , Animals , Male , Drug-Seeking Behavior/physiology , Drug-Seeking Behavior/drug effects , Rats , Serotonin/metabolism , Female , Cocaine/administration & dosage , Cocaine/pharmacology , Hippocampus/metabolism , Hippocampus/drug effects , Pyridines/pharmacology , Serotonin Antagonists/pharmacology , Signal Transduction/drug effects , Signal Transduction/physiology , Piperazines/pharmacology , Rats, Sprague-Dawley , Cocaine-Related Disorders/metabolism , Cocaine-Related Disorders/psychology , Self Administration , Extinction, Psychological/drug effects , Extinction, Psychological/physiology , Receptor, Serotonin, 5-HT1B/metabolism , CA1 Region, Hippocampal/drug effects , CA1 Region, Hippocampal/metabolism
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