RESUMEN
Rhabdomyolysis is one of the principal causes of acute kidney disease. Multiple endogenous and exogenous causes could start this process: cocaine addiction, a social phenomenon present in our Country among young adults, is one exogenous causes. Natural stimulating alkaloid cocaine has toxic action on multiple systems, principally central nervous system and cardiovascular system. Etiopathogenesis is related either to changes in local and systemic hemodynamics, or to direct damage caused by myofibril accumulation, or to immunological events leading to vasculitis or thrombotic microangiopathies. Scientific evidences describe different therapeutic approaches: supportive therapy, extracorporeal treatments and possible removal of the pathogenic noxa, and the therapeutic apheresis plays a role yet to be confirmed in this field. We describe the case of a 52-year-old man, hospitalized in the Cardiological Intensive Care Unit of our hospital, due to serious alterations in the indices of myocardiocytonecrosis and liver function, following cocaine abuse. During hospitalization, renal function indices worsened associated to diuresis contraction and onset of metabolic acidosis, not responsive to medical therapy. Also in consideration of myoglobin high circulating levels, related to rhabdomyolysis, the patient went under a cycle of selective apheresis using adsorption with a TR350 cartridge associated to hemodialysis: after two adsorption sessions, the patient resumed spontaneous diuresis with progressive normalization of the blood indices.
Asunto(s)
Trastornos Relacionados con Cocaína , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Cocaína/complicaciones , Rabdomiólisis/terapia , Rabdomiólisis/inducido químicamenteRESUMEN
BACKGROUND: Cocaine-one of the most frequently abused illicit drugs among persons living with HIV [people living with HIV (PLWH)]-slows the decline of viral production after antiretroviral therapy and is associated with higher HIV viral load, more rapid HIV progression, and increased mortality. SETTING: We examined the impact of cocaine use on the CD4+ T-cell HIV latent reservoir (HLR) in virally suppressed PLWH participating in a national, longitudinal cohort study of the natural and treated history of HIV in the United States. METHODS: CD4+ T-cell genomic DNA from 434 women of diverse ancestry (ie, 75% Black, 14% Hispanic, 12% White) who self-reported cocaine use (ie, 160 cocaine users, 59 prior users, 215 non-users) was analyzed using the Intact Proviral HIV DNA Assay, measuring intact provirus per 106 CD4+ T cells. FINDINGS: HIV latent reservoir size differed by cocaine use (ie, median [interquartile range]: 72 [14-193] for never users, 165 [63-387] for prior users, 184 [28-502] for current users), which was statistically significantly larger in both prior (P = 0.023) and current (P = 0.001) cocaine users compared with never users. CONCLUSIONS: Cocaine use may contribute to a larger replication competent HLR in CD4+ T cells among virologically suppressed women living with HIV. Our findings are important because women are underrepresented in HIV reservoir studies and in studies of the impact of cocaine use on outcomes among PLWH.
Asunto(s)
Linfocitos T CD4-Positivos , Trastornos Relacionados con Cocaína , Infecciones por VIH , Carga Viral , Latencia del Virus , Humanos , Femenino , Infecciones por VIH/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Trastornos Relacionados con Cocaína/epidemiología , Estudios Longitudinales , VIH-1/genética , Estados Unidos/epidemiología , ADN Viral , CocaínaRESUMEN
Orbital cellulitis is a common ophthalmologic consultation and has numerous risk factors; however, one that is seldomly encountered is chronic cocaine use. We describe a case of a 63-year-old man with a history of HIV and cocaine use who presented with OD pain, proptosis, and blurred vision. CT imaging revealed extensive erosions throughout the nasal septum, bilateral turbinates, ethmoid sinuses, and loss of the right medial orbital wall. The patient was treated empirically with broad-spectrum antibiotics, and a nasal biopsy and culture grew Staphylococcus aureus. After treatment with IV antibiotics, the patient's visual acuity returned to baseline with resolution of extraocular motility limitations. Although nasal erosions are a well-described sequela of cocaine use, full-thickness osseous defects of the orbital wall are rare and represent late-stage complications of cocaine-induced destructive midline lesions. Orbital cellulitis is a very rare complication in the setting of cocaine-induced destructive midline lesions. Clinicians should be aware of the link between cocaine use, rhino-orbital abnormalities, and orbital cellulitis.
Asunto(s)
Trastornos Relacionados con Cocaína , Celulitis Orbitaria , Tomografía Computarizada por Rayos X , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Cocaína/complicaciones , Celulitis Orbitaria/diagnóstico , Celulitis Orbitaria/inducido químicamente , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Bacterianas del Ojo/diagnóstico , Antibacterianos/efectos adversos , Staphylococcus aureus/aislamiento & purificación , Cocaína/efectos adversosRESUMEN
BACKGROUND: Cocaine use (CU) is prevalent in people with HIV (PWH). Both conditions are linked to changes in cognitive functioning and neural network topology. The current study utilizes graph theory to investigate functional connectomics associated with HIV and CU, focusing on disruption of densely connected nodes called hubs. METHODS: Resting state functional magnetic resonance imaging (fMRI) from 206 adults (ages 22-55 years) were analyzed. A HIV x CU factorial design was implemented with participants in four groups: HIV+CU (n= 41), HIV only (n= 88), CU only (n= 36), and controls (n= 41). Functional connectomes were constructed, and thresholded graph metrics were calculated. Network centrality metrics - betweenness centrality (BC), participation coefficient (PC), and within module degree (WD) - were quantified into hub disruption indices (HDI). For each index, a 2×2 ANCOVA was performed controlling for education. RESULTS: Participants were 68 % male and 74 % African-American with a mean age of 44.4 years. HIV and CU were associated with hub disruption in all three indices. Interactions were significant for HDI-PC and HDI-WD, such that HIV disease was associated with greater hub disruption among participants without CU, but not among participants with CU. Overall, lower global cognitive functioning was associated with greater hub disruption on all three indices. CONCLUSIONS: Widespread hub disruption was evident in HIV disease and CU, highlighting topological reorganization in both diseases with neurocognitive effects. Hub-related measures inform functional connectivity disruptions in HIV disease and CU, particularly with respect to changes in network topology throughout the connectome.
Asunto(s)
Encéfalo , Trastornos Relacionados con Cocaína , Conectoma , Infecciones por VIH , Imagen por Resonancia Magnética , Humanos , Masculino , Adulto , Femenino , Infecciones por VIH/psicología , Persona de Mediana Edad , Trastornos Relacionados con Cocaína/diagnóstico por imagen , Trastornos Relacionados con Cocaína/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Adulto Joven , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatologíaRESUMEN
Substance use disorder (SUD) is a heterogeneous disorder, where severity, symptoms, and patterns of use vary across individuals. Yet, when rats self-administer cocaine under short-access conditions, their behavior tends to be well-regulated, though individual differences can emerge with long- or intermittent-access. In contrast, significant individual differences emerge when rats self-administer 3,4-methylenedioxypyrovalerone (MDPV), even under short-access conditions, wherein ~30 % of rats exhibit high levels of drug-taking. This study assessed SUD-like phenotypes of male and female rats self-administering MDPV or cocaine by comparing level of drug intake, responding during periods of signaled drug unavailability, and sensitivity to footshock punishment to determine whether: (1) under short-access conditions, rats that self-administer MDPV will exhibit a more robust SUD-like phenotype than rats that self-administer cocaine; (2) female rats will have a more severe phenotype than male rats; and (3) compared to short-access, long- and intermittent-access to MDPV or cocaine self-administration will result in a more robust SUD-like phenotype. Compared to cocaine, rats that self-administered MDPV exhibited a more severe phenotype, even under short-access conditions. Long- and intermittent-access to cocaine and MDPV temporarily altered drug-taking patterns but did not systematically change SUD-like phenotypes. Behavioral and quantitative autoradiography studies suggest phenotypic differences are not due to expression of dopamine transporter, dopamine D2 or D3 receptors, or 5-HT1B, 5-HT2A, or 5-HT2C receptors. This study suggests individuals who use synthetic cathinones may be at greater risk for developing a SUD, and short-access MDPV self-administration may provide a useful method to study the transition to disordered substance use in humans.
Asunto(s)
Benzodioxoles , Cocaína , Fenotipo , Pirrolidinas , Autoadministración , Cathinona Sintética , Animales , Benzodioxoles/administración & dosificación , Femenino , Masculino , Ratas , Pirrolidinas/administración & dosificación , Cocaína/administración & dosificación , Trastornos Relacionados con Sustancias/psicología , Ratas Sprague-Dawley , Caracteres Sexuales , Trastornos Relacionados con CocaínaRESUMEN
There is a high prevalence of antisocial personality disorder (ASPD) in individuals affected by substance use disorders (SUD). However, there is limited information on the specific patterns of association of ASPD with SUD severity and specific SUD diagnostic criteria. We investigated the association of alcohol, cannabis, cocaine, opioid, and tobacco use disorders (AUD, CanUD, CocUD, OUD, and TUD, respectively) in 1660 individuals with ASPD and 6640 controls matched by sex (24% female), age, and racial/ethnic background in a sample ascertained for addiction-related traits. Generalized linear regressions were used to test ASPD with respect to the five DSM-5 SUD diagnoses, their severity (i.e., mild, moderate, severe), and their diagnostic criteria. We found that ASPD is associated with the diagnosis and severity of AUD (Odds Ratio, ORs = 1.89 and 1.25), CanUD (ORs = 2.13 and 1.32), and TUD (ORs = 1.50 and 1.21) (ps < 0.003). Of the specific diagnostic criteria, the "hazardous use" criterion showed the strongest association with ASPD across the five SUDs investigated (from ORTUD = 1.88 to ORCanUD = 1.37). However, when criteria of different SUDs were included in the same model, ASPD was independently associated only with TUD "hazardous use" and CocUD "attempts to quit". Attempting to quit cocaine was inversely related to the presence of ASPD and remained significant (OR = 0.57, 95% confidence interval = 0.36-0.89) after controlling for interactive effects with sex. The current work provides novel insights into ASPD-SUD comorbidity, supporting the existence of different SUD patterns among individuals affected by ASPD.
Asunto(s)
Trastorno de Personalidad Antisocial , Comorbilidad , Trastornos Relacionados con Sustancias , Humanos , Masculino , Femenino , Trastorno de Personalidad Antisocial/epidemiología , Adulto , Trastornos Relacionados con Sustancias/epidemiología , Persona de Mediana Edad , Estudios de Casos y Controles , Adulto Joven , Trastornos Relacionados con Cocaína/epidemiología , Índice de Severidad de la Enfermedad , Manual Diagnóstico y Estadístico de los Trastornos MentalesRESUMEN
Over the years, the growing "epidemic" spread of cocaine use represents a crucial public health and social problem worldwide. According to the 2023 World Drug Report, 0.4% of the world's population aged 15 to 64 report using cocaine; this number corresponds to approximately 24.6 million cocaine users worldwide and approximately 1 million subjects with cocaine use disorder (CUD). While we specifically know the short-term side effects induced by cocaine, unfortunately, we currently do not have exhaustive information about the medium/long-term side effects of the substance on the body. The scientific literature progressively highlights that the chronic use of cocaine is related to an increase in cardio- and cerebrovascular risk and probably to a greater incidence of psychomotor symptoms and neurodegenerative processes. Several studies have highlighted an increased risk of antipsychotic-induced extrapyramidal symptoms (EPSs) in patients with psychotic spectrum disorders comorbid with psychostimulant abuse. EPSs include movement dysfunction such as dystonia, akathisia, tardive dyskinesia, and characteristic symptoms of Parkinsonism such as rigidity, bradykinesia, and tremor. In the present paper, we propose a model of interpretation of the neurobiological mechanisms underlying the hypothesized increased vulnerability in chronic cocaine abusers to neurodegenerative disorders with psychomotor symptoms. Specifically, we supposed that the chronic administration of cocaine produces significant neurobiological changes, causing a complex dysregulation of various neurotransmitter systems, mainly affecting subcortical structures and the dopaminergic pathways. We believe that a better understanding of these cellular and molecular mechanisms involved in cocaine-induced neuropsychotoxicity may have helpful clinical implications and provide targets for therapeutic intervention.
Asunto(s)
Trastornos Relacionados con Cocaína , Cocaína , Enfermedad de Parkinson , Humanos , Trastornos Relacionados con Cocaína/epidemiología , Cocaína/toxicidad , Cocaína/efectos adversos , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/epidemiologíaRESUMEN
Repeated cocaine use produces adaptations in brain function that contribute to long-lasting behaviors associated with cocaine use disorder (CUD). In rodents, the activity-regulated cytoskeleton-associated protein (Arc) can regulate glutamatergic synaptic transmission, and cocaine regulates Arc expression and subcellular localization in multiple brain regions, including the nucleus accumbens (NAc)-a brain region linked to CUD-related behavior. We show here that repeated, non-contingent cocaine administration in global Arc KO male mice produced a dramatic hypersensitization of cocaine locomotor responses and drug experience-dependent sensitization of conditioned place preference (CPP). In contrast to the global Arc KO mice, viral-mediated reduction of Arc in the adult male, but not female, NAc (shArcNAc) reduced both CPP and cocaine-induced locomotor activity, but without altering basal miniature or evoked glutamatergic synaptic transmission. Interestingly, cell type-specific knockdown of Arc in D1 dopamine receptor-expressing NAc neurons reduced cocaine-induced locomotor sensitization, but not cocaine CPP; whereas, Arc knockdown in D2 dopamine receptor-expressing NAc neurons reduced cocaine CPP, but not cocaine-induced locomotion. Taken together, our findings reveal that global, developmental loss of Arc produces hypersensitized cocaine responses; however, these effects cannot be explained by Arc's function in the adult mouse NAc since Arc is required in a cell type- and sex-specific manner to support cocaine-context associations and locomotor responses.
Asunto(s)
Cocaína , Proteínas del Citoesqueleto , Proteínas del Tejido Nervioso , Núcleo Accumbens , Animales , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efectos de los fármacos , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Masculino , Ratones , Femenino , Cocaína/farmacología , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D1/genética , Locomoción/efectos de los fármacos , Trastornos Relacionados con Cocaína/metabolismo , Trastornos Relacionados con Cocaína/genética , Trastornos Relacionados con Cocaína/fisiopatología , Ratones Endogámicos C57BL , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Transmisión SinápticaRESUMEN
The comorbidity between cocaine use disorder (CUD) and trauma/stressor-related disorders suggests a connection between neurophysiological changes induced by stress and those that lead to cocaine use. Due to the unexpected and sometimes uncontrollable nature and timing of stressful life events, their capacity to induce drug use poses a significant challenge for the administration of cocaine relapse therapy. This study aims to investigate the impact of chronic stress applied prior to cocaine acquisition on the development of cocaine-seeking behavior after different periods of drug abstinence in male and female rats. Rats were exposed to five days of inescapable footshocks (chronic stress) before undergoing extended access cocaine self-administration. Different groups then underwent forced abstinence periods of 1, 15, or 30 days before cue- and cocaine-induced seeking tests. Results showed that, after 30 days of abstinence, stressed females exhibited higher cue-induced, but not cocaine-induced seeking, compared to female controls and to males. In contrast, at 30 days, stressed males showed higher cocaine-, but not cue-induced seeking, versus controls. Such sex-dependent alterations in motivation and drug effects following prolonged abstinence highlight the importance of considering sex-specific differences in stress-related addiction research. Ongoing work should evaluate other stressors and self-administration models to elucidate neurophysiological and hormonal mechanisms underlying the incubation of cocaine craving. Identifying shared pathways between chronic stress and addiction could offer novel strategies for treating trauma/stress-related substance use disorders in a sex-specific manner.
Asunto(s)
Trastornos Relacionados con Cocaína , Cocaína , Señales (Psicología) , Comportamiento de Búsqueda de Drogas , Recurrencia , Autoadministración , Caracteres Sexuales , Estrés Psicológico , Animales , Masculino , Femenino , Estrés Psicológico/fisiopatología , Cocaína/farmacología , Cocaína/administración & dosificación , Trastornos Relacionados con Cocaína/fisiopatología , Ratas , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Comportamiento de Búsqueda de Drogas/fisiología , Inhibidores de Captación de Dopamina/farmacología , Inhibidores de Captación de Dopamina/administración & dosificación , Síndrome de Abstinencia a Sustancias/fisiopatologíaRESUMEN
The dopamine transporter has a crucial role in regulation of dopaminergic neurotransmission by uptake of dopamine into neurons and contributes to the abuse potential of psychomotor stimulants1-3. Despite decades of study, the structure, substrate binding, conformational transitions and drug-binding poses of human dopamine transporter remain unknown. Here we report structures of the human dopamine transporter in its apo state, and in complex with the substrate dopamine, the attention deficit hyperactivity disorder drug methylphenidate, and the dopamine-uptake inhibitors GBR12909 and benztropine. The dopamine-bound structure in the occluded state precisely illustrates the binding position of dopamine and associated ions. The structures bound to drugs are captured in outward-facing or inward-facing states, illuminating distinct binding modes and conformational transitions during substrate transport. Unlike the outward-facing state, which is stabilized by cocaine, GBR12909 and benztropine stabilize the dopamine transporter in the inward-facing state, revealing previously unseen drug-binding poses and providing insights into how they counteract the effects of cocaine. This study establishes a framework for understanding the functioning of the human dopamine transporter and developing therapeutic interventions for dopamine transporter-related disorders and cocaine addiction.
Asunto(s)
Benzotropina , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Inhibidores de Captación de Dopamina , Dopamina , Humanos , Apoproteínas/metabolismo , Apoproteínas/química , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Benzotropina/metabolismo , Benzotropina/farmacología , Sitios de Unión , Cocaína/farmacología , Cocaína/metabolismo , Trastornos Relacionados con Cocaína/tratamiento farmacológico , Dopamina/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/antagonistas & inhibidores , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/química , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Inhibidores de Captación de Dopamina/metabolismo , Inhibidores de Captación de Dopamina/farmacología , Metilfenidato/metabolismo , Metilfenidato/farmacología , Modelos Moleculares , Piperazinas/metabolismo , Piperazinas/farmacología , Unión Proteica , Conformación ProteicaRESUMEN
Cocaine use disorder is a condition that leads to tremendous morbidity and mortality for which there are currently no FDA-approved pharmacotherapies. Previous research has demonstrated an important role for the resident population of bacteria of the large intestine, collectively dubbed the gut microbiome, in modulating brain and behavior in models of cocaine and other substance use disorders. Importantly, previous work has repeatedly shown that depletion of the gut microbiome leads to increased cocaine taking and seeking behaviors in multiple models. While the precise mechanism of these gut-brain signaling pathways in models of cocaine use is not fully clear, and intriguing possibility is through gut microbiome influences on innate immune system function. In this manuscript we identify the cytokine colony stimulating factor 2 (CSF2) as an immune factor that is increased by cocaine in a gut microbiome dependent manner. Peripherally injected CSF2 crosses the blood-brain barrier into the nucleus accumbens, a brain region central to behavioral responses to cocaine. Treatment with peripheral CSF2 reduces acute and sensitized locomotor responses to cocaine as well as reducing cocaine place preference at high doses. On a molecular level, we find that peripheral injections of CSF2 alter the transcriptional response to both acute and repeated cocaine in the nucleus accumbens. Finally, treatment of microbiome depleted mice with CSF2 reverses the behavioral effects of microbiome depletion on the conditioned place preference assay. Taken together, this work identifies an innate immune factor that represents a novel gut-brain signaling cascade in models of cocaine use and lays the foundations for further translational work targeting this pathway.
Asunto(s)
Trastornos Relacionados con Cocaína , Cocaína , Microbioma Gastrointestinal , Animales , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/fisiología , Cocaína/farmacología , Cocaína/administración & dosificación , Ratones , Trastornos Relacionados con Cocaína/metabolismo , Trastornos Relacionados con Cocaína/microbiología , Ratones Endogámicos C57BL , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Locomoción/efectos de los fármacosRESUMEN
INTRODUCTION: To understand the influence of phenotypic characteristics, such as stress, on substance use treatment outcomes, measures must function equivalently across groups to allow for interpretable comparisons of effects. The present study evaluated measurement invariance of the Perceived Stress Scale (PSS) across race, sex, and time, examined its association with cocaine use disorder (CUD) treatment outcomes, and tested whether associations were moderated by race and/or sex. METHODS: Data from four clinical trials evaluating behavioral and/or pharmacological treatments for cocaine use were combined providing a total sample of 302 participants with DSM-IV cocaine abuse/dependence (57.6 % Black, 42.4 % White, 43.7 % females, Mage = 40.22 years, SD = 9.26). RESULTS: Factor analyses support a two-factor model (i.e., general stress, self-efficacy to cope with stressors) that demonstrated configural, metric, and scalar invariance across race and sex and configural and metric invariance across time. End-of-treatment stress and coping were both related to treatment outcomes, but not treatment retention. Interactions between baseline and end-of-treatment stress and coping self-efficacy with race and sex predicting treatment retention and outcomes were not significant. CONCLUSIONS: Results support the utility of the PSS to examine between-group differences among individuals with CUD and suggest that sociodemographic groups differ in the extent to which stress and self-efficacy to cope influence treatment outcomes.
Asunto(s)
Trastornos Relacionados con Cocaína , Estrés Psicológico , Humanos , Trastornos Relacionados con Cocaína/psicología , Trastornos Relacionados con Cocaína/terapia , Femenino , Masculino , Adulto , Estrés Psicológico/psicología , Resultado del Tratamiento , Factores Sexuales , Adaptación Psicológica , Población Blanca/psicología , Factores de Tiempo , Autoeficacia , Persona de Mediana Edad , Negro o Afroamericano/psicología , Pruebas Psicológicas , AutoinformeRESUMEN
The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.
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Cocaína , ADN Mitocondrial , Hipuratos , Hepatopatías Alcohólicas , Proteínas de la Membrana , Transducción de Señal , Animales , Cocaína/farmacología , Cocaína/toxicidad , Transducción de Señal/efectos de los fármacos , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/patología , ADN Mitocondrial/metabolismo , ADN Mitocondrial/efectos de los fármacos , Ratones , Hipuratos/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Macrófagos del Hígado/efectos de los fármacos , Macrófagos del Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Etanol/toxicidad , Ratones Endogámicos C57BL , Trastornos Relacionados con Cocaína/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismoRESUMEN
We describe a patient who developed lip necrosis and a nasal septal defect after excessively nasal abuse of cocaine. Necrosis of the lip can be caused by local vasoconstriction of the vessels of the skin, by the anesthetic effects of cocaine, by local irritation and inflammation and by the effects of adulterants. The patient was unable to stop using cocaine on her own and was compulsorily admitted. The surgical reconstruction of the lip was planned, but not performed because of the constant use of cocaine.
Asunto(s)
Trastornos Relacionados con Cocaína , Labio , Necrosis , Humanos , Trastornos Relacionados con Cocaína/complicaciones , Femenino , Labio/patología , Necrosis/inducido químicamente , AdultoRESUMEN
This study aims to describe movement disorders secondary to cocaine use. To our knowledge, while these presentations have been previously reported in the literature, a comprehensive review has not been published yet. We searched six databases from 1986 to 2022 without language restriction. Case reports, case series, and literature reviews have been analysed to find associations between cocaine use and movement disorders. The present study encompasses epidemiology, clinical manifestations, pathophysiology, and diagnostic challenges of abnormal movements associated with cocaine use. This review highlights the importance of proper initial evaluation and investigation taking into account the broad spectrum of differential diagnoses and exclusion of primary movement disorders. The role of the dopaminergic system in movement disorders is reviewed. Cocaine use is associated with movement disorders such as dystonia, parkinsonism, akathisia, and tics. The complex interaction of multiple factors, including other neurological conditions, such as Tourette syndrome, and additional substances of abuse is discussed. The presentation of these manifestations is often heterogeneous and does not follow a specific pattern. In this way, future research is needed to improve our understanding of the pathophysiological mechanisms and develop novel drug targets for these disorders. Increased awareness among the general public and policymakers could translate into reduced stigma and improved care.
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Trastornos del Movimiento , Humanos , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/etiología , Trastornos del Movimiento/fisiopatología , Trastornos Relacionados con Cocaína/complicaciones , Trastornos Relacionados con Cocaína/epidemiología , Cocaína/efectos adversosRESUMEN
INTRODUCTION: Over the past decade, frequent use of large quantities of nitrous oxide (N2O) has become more common in the Netherlands. Although N2O poses several negative health consequences for a subgroup of problematic N2O users, there is a lack of knowledge on what characterizes these intensive users. This study therefore aims to provide the demographic and substance use characteristics and experiences during treatment of treatment seeking problematic N2O users and to compare this with a matched group of treatment-seeking problematic cocaine users. METHODS: A retrospective chart review was performed of patients who were referred for treatment of problematic N2O use at a large Dutch addiction care facility from January 2020 to September 2022, extracting demographics, pattern of use and follow-up data. Additionally, a subgroup of N2O users was propensity-score matched (1:1) with a subgroup of treatment seeking problematic cocaine users, both groups excluding users with substance use disorders or frequent use of substances other than N2O and cocaine, respectively. RESULTS: 128 patients with a N2O use disorder were included in the total sample and a subgroup of 77 N2O-only users was propensity-score matched on age and sex to 77 cocaine-only users. N2O users were typically young (mean age 26.2 years), male (66.4%), unmarried (82.9%), with a low education level (59.0%) and born in the Netherlands (88.2%), with parents born in Morocco (45.3%). N2O was used intermittently (median 10 days/month, IQR 4.0-17.5 days) and often in very large quantities (median 5 kg [ca. 750 balloons] per average using day, IQR 2-10 kg). Compared to the patients with a cocaine use disorder, matched N2O users were lower educated, more often from Moroccan descent, and less likely to be alcohol or polysubstance users. Despite receiving similar treatments, N2O users were twice as likely to discontinue treatment before completion compared to cocaine users (63 vs. 35%, p = 0.004). CONCLUSION: Treatment-seeking problematic N2O users are demographically different from treatment-seeking problematic cocaine users and are much more likely to dropout from psychological treatment. Further research is needed into the needs and other factors of problematic N2O users that relate to poor treatment adherence in problematic N2O users.
Asunto(s)
Trastornos Relacionados con Cocaína , Óxido Nitroso , Humanos , Masculino , Femenino , Óxido Nitroso/uso terapéutico , Adulto , Estudios Retrospectivos , Países Bajos/epidemiología , Trastornos Relacionados con Cocaína/terapia , Trastornos Relacionados con Cocaína/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/terapia , Adulto JovenRESUMEN
Individual differences in drug use emerge soon after initial exposure, and only a fraction of individuals who initiate drug use go on to develop a substance use disorder. Variability in vulnerability to establishing drug self-administration behavior is also evident in preclinical rodent models. Latent characteristics that underlie this variability and the relationship between early drug use patterns and later use remain unclear. Here, we attempt to determine whether propensity to establish cocaine self-administration is related to subsequent cocaine self-administration behavior in male Sprague-Dawley rats (n = 14). Prior to initiating training, we evaluated basal locomotor and anxiety-like behavior in a novel open field test. We then trained rats to self-administer cocaine in daily 3â¯h cocaine (0.75â¯mg/kg/infusion) self-administration sessions until acquisition criteria (≥30 active lever presses with ≥70â¯% responding on the active lever in one session) was met and divided rats into Early and Late groups by median-split analysis based on their latency to meet acquisition criteria. After each rat met acquisition criteria, we gave them 10 additional daily cocaine self-administration sessions. We then conducted a progressive ratio, cocaine-induced locomotor sensitivity test, and non-reinforced cocaine seeking test after two weeks of forced abstinence. Early Learners exhibited significantly less locomotion after an acute injection of cocaine, but the groups did not differ in any other behavioral parameter examined. These results indicate that cocaine self-administration acquisition latency is not predictive of subsequent drug-taking behavior, but may be linked to physiological factors like drug sensitivity that can predispose rats to learn the operant task.
Asunto(s)
Cocaína , Locomoción , Ratas Sprague-Dawley , Autoadministración , Animales , Masculino , Cocaína/farmacología , Cocaína/administración & dosificación , Ratas , Locomoción/efectos de los fármacos , Locomoción/fisiología , Inhibidores de Captación de Dopamina/farmacología , Inhibidores de Captación de Dopamina/administración & dosificación , Condicionamiento Operante/efectos de los fármacos , Condicionamiento Operante/fisiología , Trastornos Relacionados con Cocaína/fisiopatología , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Ansiedad/fisiopatología , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Comportamiento de Búsqueda de Drogas/fisiologíaRESUMEN
Addiction is a complex behavioral disorder characterized by compulsive drug-seeking and drug use despite harmful consequences. The prefrontal cortex (PFC) plays a crucial role in cocaine addiction, involving decision-making, impulse control, memory, and emotional regulation. The PFC interacts with the brain's reward system, including the ventral tegmental area (VTA) and nucleus accumbens (NAc). The PFC also projects to the lateral habenula (LHb), a brain region critical for encoding negative reward and regulating the reward system. In the current study, we examined the role of PFC-LHb projections in regulating cocaine reward-related behaviors. We found that optogenetic stimulation of the PFC-LHb circuit during cocaine conditioning abolished cocaine preference without causing aversion. In addition, increased c-fos expression in LHb neurons was observed in animals that received optic stimulation during cocaine conditioning, supporting the circuit's involvement in cocaine preference regulation. Molecular analysis in animals that received optic stimulation revealed that cocaine-induced alterations in the expression of GluA1 subunit of AMPA receptor was normalized to saline levels in a region-specific manner. Moreover, GluA1 serine phosphorylation on S845 and S831 were differentially altered in LHb and VTA but not in the PFC. Together these findings highlight the critical role of the PFC-LHb circuit in controlling cocaine reward-related behaviors and shed light on the underlying mechanisms. Understanding this circuit's function may provide valuable insights into addiction and contribute to developing targeted treatments for substance use disorders.