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1.
Talanta ; 237: 122904, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736717

RESUMO

In this work, we have focused on the profiling of 5647 street samples covering marijuana, common and new recreational illicit drugs. All samples were analyzed using gas chromatography-mass spectrometry (GC-MS) technique. In total we have identified 53 illicit drugs with Δ-9-tetrahydrocannabinol (THC), amphetamine, N-ethylhexedrone, 3,4-methylenedioxy methamphetamine (MDMA), 4-chloromethcathinone (4-CMC), α-pyrrolidinoisohexaphenone (α-PHiP), cocaine, and 4-chloroethcathinone (4-CEC) being most commonly found and making 38.5, 17.8, 15.5, 8.0, 3.5, 2.7, 2.1, and 2.0% of the total studied pool, respectively. Except for methadone, all analyzed street samples were spiked with at least one cutting agent. Caffeine was the most frequently found adulterating addition present in around 33% (excluding marijuana) of the analyzed samples. Other identified cutting agents make an impressive group of more than 160 compounds. Finally, we have tabulated, illustrated, and discussed presented data in a view of smart and portable sensors development.


Assuntos
Cocaína , Drogas Ilícitas , Metanfetamina , Anfetamina/análise , Cocaína/análise , Cromatografia Gasosa-Espectrometria de Massas , Metanfetamina/análise , Detecção do Abuso de Substâncias
2.
Anal Chim Acta ; 1187: 339141, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34753574

RESUMO

Natural and synthetic alkaloids are widely used for several applications, ranging from clinical purposes to criminal activities. Presumptive color tests are considered a leading tool to reveal on-scene substance identification via rapid chemical reactions that result in visual color changes. Colorimetric tests are popular due to their inherent simplicity, low cost, promptitude and portability; however, in many cases the results of such tests may not be predictable, partly because of the interference from similar species. In this proof-of-concept study, we present a paper-based microfluidic optoelectronic tongue - the so-called µOPTO - comprised of 6 indicators in lieu of one specific test and capable of discriminating 8 different alkaloid drugs (i.e. scopolamine, atropine, cocaine, morphine, ephedrine, caffeine, dipyrone and alprazolam) used for recreational, criminal and medical purposes. The wax printing method was employed to fabricate the microfluidic analytical device with six circular spots for reagent accommodation connected to a centered spot to enable simultaneous reactions with one sample injection. Digital images were obtained using an ordinary flatbed scanner, and the RGB information from before and after sample exposure was extracted using appropriate software. The color changes related to each spot were used to build differential maps with a unique fingerprint for each drug. The chemometric tools (i.e. PCA and HCA) showed suitable discrimination of all studied alkaloids in different quantities. To demonstrate a practical application, different alcoholic beverages spiked with scopolamine - a famous substance that causes drug abuse - were analyzed using the optoelectronic tongue. The results showed that small quantities of the drug were identified in different beverages, demonstrating that our device has the potential to be used in situ to prevent ingestion of contaminated samples.


Assuntos
Cocaína , Preparações Farmacêuticas , Colorimetria , Microfluídica , Língua
3.
J Hist Dent ; 69(2): 94-98, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34734789

RESUMO

For decades dentists have faced the challenge of achieving profound anesthesia in the presence of a severe tooth ache. Frequently this challenge was more acute when the tooth or teeth in question were mandibular molars. Over a 125 years ago this clinical dilemma was managed by using cocaine, both directly on an exposed dental pulp and often times using a solution of such injected directly into the pulp. Both clinical applications were considered as achieving "pressure anesthesia" sufficient to permit pulp extirpation. This historical perspective will focus on both the origins of this approach and its contemporary counterparts.


Assuntos
Anestesia Dentária , Anestesiologia , Cocaína , Dente Molar , Pulpectomia
4.
J Invasive Cardiol ; 33(11): E922, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34735360

RESUMO

Septal branches arising from the left anterior descending coronary artery supply the anterior interventricular septum in unison. In this unusual presentation of cocaine heart disease, occlusion of a single dominant septal perforator caused a large septal myocardial infarction, resulting in significant left ventricular impairment.


Assuntos
Cocaína , Infarto do Miocárdio , Cocaína/efeitos adversos , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Septos Cardíacos/diagnóstico por imagem , Septos Cardíacos/cirurgia , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia
5.
J Investig Med High Impact Case Rep ; 9: 23247096211051921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34663104

RESUMO

Intestinal ischemia results from diminished perfusion of the colon resulting in tissue hypoxia. Anecdotal reports suggest that cocaine-induced intestinal ischemia has the highest mortality and longer length of stay among the vasoconstrictors. The present study aimed to summarize the available studies in the literature to assess the effect of routes of consumption on the outcomes of cocaine-induced intestinal ischemia. We conducted a systematic search of MEDLINE from inception through October 2019. Studies of cocaine-induced intestinal ischemia were included if data were available on comorbidities, mortality, and hospital length of stay (LOS). The study's primary outcomes were mortality and need for surgery, while secondary outcomes included the hospital length of stay, LACE index, and hospital score. Statistical tests used included linear and binary logistic regression. STATA 2015 was used, and P < 0.05 was statistically significant. Of the 304 studies, 8 case series and 45 case reports (n = 69 patients) met the inclusion criteria. Different routes of cocaine use had similar mortality odds and the need for surgery for intestinal ischemia. Hospital LOS showed significant difference among the subgroups. Readmission scores (LACE and hospital score) were higher for intravenous and smoking than ingestion and intranasal use (P < 0.05). In conclusion, different routes of cocaine use appear to have similar mortality odds for intestinal ischemia, which vary significantly among the different routes of cocaine consumption for the length of stay and readmission scores. Prompt recognition of the route of cocaine use is vital to improve the outcome. Large-scale and well-designed observational studies are needed to investigate this topic further.


Assuntos
Cocaína , Cocaína/efeitos adversos , Comorbidade , Humanos , Isquemia , Tempo de Internação
6.
Analyst ; 146(22): 6780-6787, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34636822

RESUMO

Three-dimensional (3D) dried blood spheroids form when whole blood is deposited onto hydrophobic paper and allowed to dry in ambient air. The adsorbed 3D dried blood spheroid present at the surface of the hydrophobic paper is observed to offer enhanced stability for labile analytes that would otherwise degrade if stored in the traditional two-dimensional (2D) dried blood spot method. The protective mechanism for the dried blood spheroid microsampling platform was studied using scanning electron microscopy (SEM), which revealed the presence of a passivation thin film at the surface of the spheroid that serves to stabilize the interior of the spheroid against environmental stressors. Through time-course experiments based on sequential SEM analyses, we discovered that the surface protective thin film forms through the self-assembly of red blood cells following the evaporation of water from the blood sample. The bridging mechanism of red blood cell aggregation is evident in our experiments, which leads to the distinct rouleau conformation of stacked red blood cells in less than 60 min after creating the blood spheroid. The stack of self-assembled red blood cells at the exterior of the spheroid subsequently lyse to afford the surface protective layer detected to be approximately 30 µm in thickness after three weeks of storage in ambient air. We applied this mechanistic insight to plasma and serum to enhance stability when stored under ambient conditions. In addition to physical characterization of these thin biofilms, we also used paper spray (PS) mass spectrometry (MS) to examine chemical changes that occur in the stored biofluid. For example, we present stability data for cocaine spiked in whole blood, plasma, and serum when stored under ambient conditions on hydrophilic and hydrophobic paper substrates.


Assuntos
Cocaína , Teste em Amostras de Sangue Seco , Interações Hidrofóbicas e Hidrofílicas , Espectrometria de Massas , Plasma
7.
Transl Psychiatry ; 11(1): 521, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635637

RESUMO

Cocaine addiction causes serious health problems, and no effective treatment is available yet. We previously identified a genetic risk variant for cocaine addiction in the PLCB1 gene and found this gene upregulated in postmortem brains of cocaine abusers and in human dopaminergic neuron-like cells after an acute cocaine exposure. Here, we functionally tested the contribution of the PLCB1 gene to cocaine addictive properties using Plcb1+/- mice. First, we performed a general phenotypic characterization and found that Plcb1+/- mice showed normal behavior, although they had increased anxiety and impaired short-term memory. Subsequently, mice were trained for operant conditioning, self-administered cocaine for 10 days, and were tested for cocaine motivation. After extinction, we found a reduction in the cue-induced reinstatement of cocaine-seeking behavior in Plcb1+/- mice. After reinstatement, we identified transcriptomic alterations in the medial prefrontal cortex of Plcb1+/- mice, mostly related to pathways relevant to addiction like the dopaminergic synapse and long-term potentiation. To conclude, we found that heterozygous deletion of the Plcb1 gene decreases cue-induced reinstatement of cocaine-seeking, pointing at PLCB1 as a possible therapeutic target for preventing relapse and treating cocaine addiction.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Animais , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Condicionamento Operante , Sinais (Psicologia) , Camundongos , Autoadministração
8.
Anal Chim Acta ; 1184: 339041, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34625250

RESUMO

Cocaine (Coc) is one of the illegal drugs and is harmful to digestive, immune, cardiovascular and urogenital systems. To achieve drug abuse control and legal action, it is essential to develop an effective method for cocaine analysis. In this work, an aptasensor has been developed using atom transfer radical polymerization (ATRP) based on host-guest chemistry for electrochemical analysis of cocaine. The NH2-DNA (Apt1) was immobilized on the indium tin oxide (ITO) electrode via addition reaction, and Fc-DNA (Apt2) was introduced to ITO relying on the specific recognition of cocaine. The Apt2 can initiate host-guest chemistry between Apt2 and ATRP initiators (ß-CD-Br15), then the ß-CD-Br15 further triggers ATRP. Moreover, ATRP avoids the sluggish kinetics and poor coupling capability sustained. The result shows a sensitive and selective analysis of cocaine within a linear range from 0.1 ng/mL to 10 µg/mL (R2 = 0.9985), with the detection limit down to 0.0335 ng/mL. Thus, this strategy provides a universal method for the analysis of illegal drugs.


Assuntos
Técnicas Biossensoriais , Cocaína , Técnicas Eletroquímicas , Eletrodos , Polimerização
9.
G Ital Nefrol ; 38(Suppl 77)2021 Sep 07.
Artigo em Italiano | MEDLINE | ID: mdl-34669304

RESUMO

Here we present a case of acute renal failure needing dialysis in a heroin addict patient chronically treated with Metadone. This give us the opportunity to review the renal effects of the main drugs of abuse, highlighting the shift occured from the four "old sisters" (Marijuana, Cocaine, Heroin and Amphetamine) to the news synthetic drugs (chiefly Synthetic Cathinones and Cannabinoids), that poses problems due to large diffusion, easy procurement, legal non-regulation and difficult analytical identification, raising medical and forensic questions. From a Nephrological point of view is essential to take great care over the need to diagnose this kind of pathology and to widen the search trying anyway to recognize the substances potentially involved.


Assuntos
Injúria Renal Aguda , Cocaína , Transtornos Relacionados ao Uso de Substâncias , Heroína , Humanos , Diálise Renal
10.
Ann Clin Lab Sci ; 51(5): 694-697, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34686512

RESUMO

OBJECTIVE: The conjunction of the coronavirus disease lockdown and the use of illicit drugs suggests the potential increase in drug usage and opioid deaths. Because of other studies, we felt the need to examine if the lockdown has caused a change in the drug intake of our population of substance abuse and pain management patients. MATERIALS: Urine drug testing is a strategy to reduce harm to patients in pain management and substance abuse treatment programs. We analyzed trends in the clinical drug testing patterns of urine specimens sent by substance abuse and pain clinics to monitor their patients. These specimens were tested by a national clinical laboratory using LC-MS/MS definitive methods. The time frame of these comparative observations was the past five years, including the time of the pandemic. RESULTS: The only decrease was a 30% reduction in test requests during the second quarter of 2020. Among the patients tested, positivity decreased greatly for the illicit drugs heroin and cocaine but increased for methamphetamine and fentanyl. Use of the antidepressant and anxiolytic drugs remained consistent or declined for some drugs, relative to pre-pandemic patterns. The percent of patients prescribed the opiates morphine and oxycodone decreased, while the use of hydrocodone increased. Positivity for the drug gabapentin increased greatly. The use of alcohol did not increase significantly during the lockdown period. CONCLUSION: In summary, these findings demonstrate relatively consistent drug use, with decreased positivity for high-risk drugs and dangerous drug combinations. We speculate that monitoring of these patients mitigates the possibility of drug misuse and potential overdose and is in concordance with the goals of these monitoring programs.


Assuntos
Consumo de Bebidas Alcoólicas , COVID-19/psicologia , Manejo da Dor/psicologia , Isolamento Social , Transtornos Relacionados ao Uso de Substâncias/psicologia , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Analgésicos/uso terapêutico , Antidepressivos , California/epidemiologia , Cocaína , Fentanila , Heroína , Humanos , Drogas Ilícitas , Metanfetamina , Manejo da Dor/métodos , Alcaloides de Triptamina e Secologanina , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
11.
Elife ; 102021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34608866

RESUMO

Locomotor sensitization (LS) is an early behavioral adaptation to addictive drugs, driven by the increase of dopamine in the Nucleus Accumbens (NAc). However, the effect on accumbal population activity remains elusive. Here, we used single-cell calcium imaging in mice to record the activity of dopamine-1-receptor (D1R) and dopamine-2-receptor (D2R) expressing spiny projection neurons (SPNs) during cocaine LS. Acute exposure to cocaine elevated D1R SPN activity and reduced D2R SPN activity, albeit with high variability between neurons. During LS, the number of D1R and D2R neurons responding in opposite directions increased. Moreover, preventing LS by inhibition of the ERK signaling pathway decreased the number of cocaine responsive D1R SPNs, but had little effect on D2R SPNs. These results indicate that accumbal population dichotomy is dynamic and contains a subgroup of D1R SPNs that eventually drives LS. Insights into the drug-related activity dynamics provides a foundation for understanding the circuit-level addiction pathogenesis.


Assuntos
Cocaína/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Animais , Neurônios Dopaminérgicos/metabolismo , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Núcleo Accumbens/efeitos dos fármacos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo
12.
Medicina (Kaunas) ; 57(9)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34577784

RESUMO

BACKGROUND AND OBJECTIVES: Cocaine users may present with positive antineutrophil cytoplasmic antibodies (ANCA) and severe midline destructive lesions (CIMDL) which are histologically characterized by massive apoptosis. However, histopathological and laboratory studies suggest that autoimmunity may not be the main pathogenic driver. We analyzed gene expression both in cell lines of nasal mucosa exposed to cocaine and in CIMDL patients to determine whether genetic predisposition might cause such lesions, which are observed in a minority of cocaine abusers. MATERIALS AND METHODS: The genetic expression profile of nasal mucosa exposed to cocaine was analyzed. Rare variants of expressed genes were searched in patients with CIMDL using exome sequencing and bio-informatics. RESULTS: We identified 462 genes that were induced by cocaine, mainly related to apoptosis and autophagy in response to oxidative stress. Under the hypothesis that genes linked to the phenotype are also induced by cocaine itself, a rare variants burden test was performed to select genes that were significantly enriched in rare mutations. Next, 11 cocaine abusers with CIMDL and no other relevant medical comorbidities underwent exome sequencing, and 12 genes that were significantly enriched in the burden test and present in at least 10 patients were identified. An in-depth analysis of these genes revealed their involvement in apoptosis, tissue homeostasis, autophagy, and response to oxidative stress. CONCLUSIONS: Oxidative stress and rare genetic alterations in the response to reactive oxygen species, apoptosis, autophagy, and tissue regeneration are plausible drivers of damage affecting nasal mucosa exposed to cocaine crystals and, consequently, the pathogenic mechanism behind CIMDL.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Anticorpos Anticitoplasma de Neutrófilos , Cocaína/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/genética , Expressão Gênica , Humanos
13.
Neuron ; 109(18): 2802-2804, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534452

RESUMO

Cocaine triggers gene splicing in brain reward circuits, but the mechanisms and importance of this response are unclear. In this issue of Neuron, Xu et al. (2021) show that the histone modification H3K36me3 marks genes spliced in response to cocaine and, using epigenome editing, establish a causal relationship between gene splicing and addiction-related behavioral responses.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Transtornos Relacionados ao Uso de Cocaína/genética , Humanos , Processamento de Proteína Pós-Traducional , Recompensa
14.
Neuron ; 109(18): 2943-2966.e8, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34480866

RESUMO

Neuronal alternative splicing is a key gene regulatory mechanism in the brain. However, the spliceosome machinery is insufficient to fully specify splicing complexity. In considering the role of the epigenome in activity-dependent alternative splicing, we and others find the histone modification H3K36me3 to be a putative splicing regulator. In this study, we found that mouse cocaine self-administration caused widespread differential alternative splicing, concomitant with the enrichment of H3K36me3 at differentially spliced junctions. Importantly, only targeted epigenetic editing can distinguish between a direct role of H3K36me3 in splicing and an indirect role via regulation of splice factor expression elsewhere on the genome. We targeted Srsf11, which was both alternatively spliced and H3K36me3 enriched in the brain following cocaine self-administration. Epigenetic editing of H3K36me3 at Srsf11 was sufficient to drive its alternative splicing and enhanced cocaine self-administration, establishing the direct causal relevance of H3K36me3 to alternative splicing of Srsf11 and to reward behavior.


Assuntos
Processamento Alternativo/fisiologia , Comportamento Aditivo/metabolismo , Cromatina/metabolismo , Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Recompensa , Processamento Alternativo/efeitos dos fármacos , Animais , Comportamento Aditivo/genética , Comportamento Aditivo/psicologia , Cromatina/genética , Epigênese Genética/efeitos dos fármacos , Epigênese Genética/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Autoadministração
15.
Drug Alcohol Depend ; 227: 109001, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34492555

RESUMO

BACKGROUND: Drug overdose deaths involving stimulants, including cocaine and psychostimulants with abuse potential (e.g., methamphetamine), have been increasing, partly because of co-involvement with opioids. Stimulant-involved overdose deaths have disproportionately increased among non-Hispanic Black (Black) and non-Hispanic American Indian/Alaskan Native (AI/AN) persons; however, the role of opioids in exacerbating disproportionate stimulant-involved death rates is unclear. METHODS: Analysis of National Vital Statistics System multiple cause-of-death mortality files examined age-adjusted cocaine- and psychostimulant-involved death rates. Analyses of death rates stratified by racial and ethnic group and opioid co-involvement included: 1) Joinpoint regression of 2004-2019 trends, 2) changes in rates from 2018 to 2019, and 3) demographic and geographic characteristics of 2019 deaths. RESULTS: From 2004 to 2019, cocaine and psychostimulant-involved death rates were higher for Black and AI/AN persons, respectively. Among all groups, increases in cocaine-involved overdose rates were largely driven by opioid co-involvement, particularly after 2013. From 2004 to 2019, rates for psychostimulant-involved deaths increased with and without opioid co-involvement. Rates for overdoses co-involving cocaine and synthetic opioids increased from 2018 to 2019 for Hispanic, non-Hispanic White (White), and Black persons. Psychostimulant-involved overdose rates with and without synthetic opioid co-involvement increased among Hispanic, White, and Black persons. In 2019, Black and AI/AN persons continued to experience higher cocaine- and psychostimulant-involved death rates, respectively. CONCLUSIONS: Stimulant-involved deaths continue to increase, and the role of opioids in driving these deaths varies by race and ethnicity. Ensuring equitable access to proven prevention and treatment interventions and incorporating social determinants of health into future research around effective pharmacotherapies may help reduce stimulant-involved overdose deaths.


Assuntos
Estimulantes do Sistema Nervoso Central , Cocaína , Overdose de Drogas , Analgésicos Opioides , Grupos Étnicos , Humanos , Estados Unidos/epidemiologia
16.
Langmuir ; 37(40): 11939-11947, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34591480

RESUMO

The cocaine aptamer was later found to bind quinine with an even higher affinity. In this work, we used a fluorescently labeled aptamer named MN4 to study its adsorption by gold nanoparticles (AuNPs), and the subsequent displacement by the nonlabeled aptamer and by quinine. Without washing, 14% of the preadsorbed MN4 strands were displaced by 4000-fold excess of free MN4, whereas no displacement was observed after washing, suggesting that washing removed weakly adsorbed aptamers. In a previous paper, rapid exchange was observed with NMR by directly mixing AuNPs and concentrated MN4, and our work has unified the dilute and concentrated aptamer conditions. The difference is attributable to the conformation of the adsorbed aptamer, where dilute aptamers are adsorbed in a collapsed state with a much higher affinity to AuNPs. In addition, the preadsorbed MN4 aptamer cannot be desorbed by adding quinine, indicating that direct desorption-based fluorescent sensors cannot be made. Finally, based on the similar color responses to both the aptamer and its nonbinding mutants, the label-free colorimetric detection method cannot be directly applied for the detection of quinine. This work indicated that different experimental conditions need to be carefully compared to have a unified understanding of aptamer/AuNP systems.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Cocaína , Nanopartículas Metálicas , Colorimetria , Ouro , Quinina
17.
Eur J Neurosci ; 54(7): 6382-6396, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34481424

RESUMO

Overdose death rates caused by psychostimulants have increased by 22.3% annually from 2008 to 2017. Cue-evoked drug craving progressively increases and contributes to perpetual relapse. Preclinical models have determined that glutamate receptor plasticity within the nucleus accumbens (NAc) drives amplified cue-evoked drug seeking after prolonged abstinence (>40 days). Isolated condition (IC) rearing increases cocaine and amphetamine (AMP) self-administration and cue-induced reinstatement. We tested the hypothesis that housing in the IC will augment AMP seeking after short and prolonged abstinence from AMP self-administration when compared with rats reared in the enrichment condition (EC). EC and IC male rats acquired stable AMP or SAL self-administration and were tested in a cue-induced AMP-seeking test after 1 and 40 days of abstinence. After the seeking test, the whole NAc was extracted and prepared for western blot analysis. Results indicate that IC rats had more active lever presses during a brief extinction interval and during the cue-induced seeking test. After 40 days of abstinence, IC rats had more active lever presses than EC rats during the cue-induced seeking test. Western blots indicated that the expression ratio between GluA1:mGlur5 was reduced only in IC-AMP-trained rats and the ratio between GluA1:mGlur1 was positively correlated with AMP seeking after prolonged abstinence in IC-AMP rats. These results indicate that IC housing engenders a vulnerable phenotype prone to persistent AMP seeking. The behavioural momentum of this vulnerable phenotype is further revealed when AMP-associated cues are presented following prolonged abstinence.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Anfetamina , Animais , Sinais (Psicologia) , Comportamento de Procura de Droga , Extinção Psicológica , Habitação , Masculino , Núcleo Accumbens , Ratos , Autoadministração
18.
Eur J Neurosci ; 54(7): 6397-6405, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505325

RESUMO

The lateral preoptic area is implicated in numerous aspects of substance use disorder. In particular, the lateral preoptic area is highly sensitive to the pharmacological properties of psychomotor stimulants, and its activity promotes drug-seeking in the face of punishment and reinstatement during abstinence. Despite the lateral preoptic area's complicity in substance use disorder, how precisely lateral preoptic area neurons signal the individual components of drug self-administration has not been ascertained. To bridge this gap, we examined how the firing of single lateral preoptic area neurons correlates with three discrete elements of cocaine self-administration: (1) drug-seeking (pre-response), (2) drug-taking (response) and (3) receipt of the cocaine infusion. A significant subset of lateral preoptic area neurons responded to each component with a mix of increases and decreases in firing-rate. A majority of these neurons signal the operant response with increases in spiking, though responses during the drug-seeking, taking and reciept windows were highly correlated.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Condicionamento Operante , Comportamento de Procura de Droga , Humanos , Neurônios , Área Pré-Óptica , Autoadministração
19.
eNeuro ; 8(5)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34544759

RESUMO

Relapse is a major challenge to the treatment of substance use disorders. A progressive increase in cue-induced drug craving, termed incubation of craving, is observed after withdrawal from multiple drugs of abuse in humans and rodents. Incubation of cocaine craving involves the strengthening of excitatory synapses onto nucleus accumbens (NAc) medium spiny neurons via postsynaptic accumulation of high-conductance Ca2+-permeable AMPA receptors. This enhances reactivity to drug-associated cues and is required for the expression of incubation. Additionally, incubation of cocaine craving is associated with loss of the synaptic depression normally triggered by stimulation of metabotropic glutamate receptor 5 (mGlu5), leading to endocannabinoid production, and expressed presynaptically via cannabinoid receptor 1 activation. Previous studies have found alterations in mGlu5 and Homer proteins associated with the loss of this synaptic depression. Here we conducted coimmunoprecipitation studies to investigate associations of diacylglycerol lipase-α (DGL), which catalyzes formation of the endocannabinoid 2-arachidonylglycerol (2-AG), with mGlu5 and Homer proteins. Although these interactions were unchanged in the NAc core at incubation-relevant withdrawal times, the association of DGL with total and phosphorylated Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) and CaMKIIß was increased. This would be predicted, based on other studies, to inhibit DGL activity and therefore 2-AG production. This was confirmed by measuring DGL enzymatic activity. However, the magnitude of DGL inhibition did not correlate with the magnitude of incubation of craving for individual rats. These results suggest that CaMKII contributes to the loss of mGlu5-dependent synaptic depression after incubation, but the functional significance of this loss remains unclear.


Assuntos
Cocaína , Síndrome de Abstinência a Substâncias , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Fissura , Lipase Lipoproteica , Núcleo Accumbens , Ratos , Ratos Sprague-Dawley
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