- Neurovascular unit alteration in somatosensory cortex and enhancement of thermal nociception induced by amphetamine involves central AT1 receptor activation. [Journal Article]
- EJEur J Neurosci 2017 Apr 27
- The use of psychostimulants, such as amphetamine (Amph), is associated with inflammatory processes, involving glia and vasculature alterations. Brain Angiotensin II (Ang II), through AT1 -receptors (...
The use of psychostimulants, such as amphetamine (Amph), is associated with inflammatory processes, involving glia and vasculature alterations. Brain Angiotensin II (Ang II), through AT1 -receptors (AT1 -R), modulates neurotransmission and plays a crucial role in inflammatory responses in brain vasculature and glia. Our aim for the present work was to evaluate the role of AT1 -R in long-term alterations induced by repeated exposure to Amph. Astrocyte reactivity, neuronal survival and brain microvascular network were analyzed at the somatosensory cortex. Thermal nociception was evaluated as a physiological outcome of this brain area. Male Wistar rats (250-320g) were administered with AT1 -R antagonist Candesartan/vehicle (3mg/kg p.o., days 1-5) and Amph/saline (2.5mg/kg i.p., days 6-10). The four experimental groups were: Veh-Sal, CV-Sal, Veh-Amph, CV-Amph. On day 17, the animals were sacrificed and their brains were processed for Nissl staining and immunohistochemistry against glial fibrillary acidic protein (GFAP) and von Willebrand factor. In another group of animals, thermal nociception was evaluated using hot plate test, in the four experimental groups, on day 17. Data were analyzed with two-way ANOVA followed by Bonferroni test. Our results indicate that Amph exposure induces an increase in: neuronal apoptosis, astrocyte reactivity and microvascular network, evaluated as an augmented occupied area by vessels, branching points and their tortuosity. Moreover, Amph exposure decreased the thermal nociception threshold. Pretreatment with the AT1 -R blocker prevented the described alterations induced by this psychostimulant. The decreased thermal nociception and the structural changes in somatosensory cortex could be considered as extended neuroadaptative responses to Amph, involving AT1 -R activation. This article is protected by copyright. All rights reserved.
- Naltrexone modulates dopamine release following chronic, but not acute amphetamine administration: a translational study. [Journal Article]
- TPTransl Psychiatry 2017 Apr 25; 7(4):e1104
- The opioid antagonist naltrexone has been shown to attenuate the subjective effects of amphetamine. However, the mechanisms behind this modulatory effect are currently unknown. We hypothesized that n...
The opioid antagonist naltrexone has been shown to attenuate the subjective effects of amphetamine. However, the mechanisms behind this modulatory effect are currently unknown. We hypothesized that naltrexone would diminish the striatal dopamine release induced by amphetamine, which is considered an important mechanism behind many of its stimulant properties. We used positron emission tomography and the dopamine D2-receptor radioligand [(11)C]raclopride in healthy subjects to study the dopaminergic effects of an amphetamine injection after pretreatment with naltrexone or placebo. In a rat model, we used microdialysis to study the modulatory effects of naltrexone on dopamine levels after acute and chronic amphetamine exposure. In healthy humans, naltrexone attenuated the subjective effects of amphetamine, confirming our previous results. Amphetamine produced a significant reduction in striatal radioligand binding, indicating increased levels of endogenous dopamine. However, there was no statistically significant effect of naltrexone on dopamine release. The same pattern was observed in rats, where an acute injection of amphetamine caused a significant rise in striatal dopamine levels, with no effect of naltrexone pretreatment. However, in a chronic model, naltrexone significantly attenuated the dopamine release caused by reinstatement of amphetamine. Collectively, these data suggest that the opioid system becomes engaged during the more chronic phase of drug use, evidenced by the modulatory effect of naltrexone on dopamine release following chronic amphetamine administration. The importance of opioid-dopamine interactions in the reinforcing and addictive effects of amphetamine is highlighted by the present findings and may help to facilitate medication development in the field of stimulant dependence.
- Chiral Analysis of Amphetamines in Hair by Liquid Chromatography-Tandem Mass Spectrometry: Compliance-Monitoring of attention deficit hyperactivity disorder (ADHD) patients under Elvanse® therapy and identification after controlled low dose application. [Journal Article]
- DTDrug Test Anal 2017 Apr 24
- Amphetamine (AMP) is used as illicit drug but also for the treatment of attention deficit hyperactivity disorder (ADHD). Respective drugs most often contain the enantiomer (S)-AMP as active compound ...
Amphetamine (AMP) is used as illicit drug but also for the treatment of attention deficit hyperactivity disorder (ADHD). Respective drugs most often contain the enantiomer (S)-AMP as active compound or (S)-AMP is formed from the prodrug lisdexamfetamine (Elvanse®) whereas the illicit drug is usually traded as racemate ((R/S)-AMP). A differentiation between the use of the medically prescribed drug and the abuse of illicit street amphetamine is of great importance e.g. in retrospective consumption monitoring by hair analysis. An LC-MS/MS method for the chiral separation and quantitation of (S)- and (R)-AMP in hair was developed. For this purpose, 20 mg hair were extracted and derivatized with N-(2,4-dinitro-5-fluorophenyl)-L(S)-valinamide L(S)-(DNPV) to yield amphetamine diastereomers. Baseline separation of the resulting diastereomers was achieved on a high pressure liquid-chromatography system (HPLC) coupled to a Sciex QTRAP® 5500 linear ion trap quadrupole mass spectrometer. The method was successfully validated. Analysis of hair samples from nine Elvanse® patients revealed only (S)-AMP in eight cases, one subject showed both enantiomers indicating a (side-) consumption of street amphetamine. The analysis of the 16 amphetamine users' samples showed only racemic amphetamine. Furthermore, it could be shown in a controlled study that (S)-AMP can be detected after administration of even very low doses of lisdexamfetamine and dexamphetamine which can be of interest in forensic toxicology and especially in drug-facilitated crimes (DFC). The method now enables the retrospective compliance-monitoring of ADHD patients and the differentiation between medically prescribed intake of (S)-amphetamine and abuse of illicit street amphetamine.
- Illicit drug use among New Zealand gay and bisexual men: Prevalence and association with sexual health behaviours. [Journal Article]
- DADrug Alcohol Rev 2017 Apr 25
- CONCLUSIONS: Drug use was common in this sample of GBM. Polydrug and methamphetamine users had especially high sexual health needs, but risks remained elevated among GBM consuming other drugs. Drug harm reduction programs and HIV prevention should target GBM with problematic drug use. Limitations include an inability to attribute causation. [Saxton P, Newcombe D, Ahmed A, Dickson N, Hughes A. Illicit drug use among New Zealand gay and bisexual men: Prevalence and association with sexual health behaviours. Drug Alcohol Rev 2017;00:000-000].
- The role of impulsivity in psychostimulant- and stress-induced dopamine release: review of human imaging studies. [Review]
- NBNeurosci Biobehav Rev 2017 Apr 21
- Drug addiction is a debilitating disorder and its pivotal problem is the high relapse rate. To solve this problem, the aim is to prevent people from becoming addicted in the first place. One of the k...
Drug addiction is a debilitating disorder and its pivotal problem is the high relapse rate. To solve this problem, the aim is to prevent people from becoming addicted in the first place. One of the key questions that is still unanswered is why some people become addicted to drugs and others, who take drugs regularly, do not. In recent years extensive research has been done to untangle the many factors involved in this disorder. Here, we review some of the factors that are related to dopamine, i.e., impulsivity and stress (hormones), and aim to integrate this into a neurobiological model. Based on this, we draw two conclusions: 1) in order to understand the transition from recreational drug use to addiction, we need to focus more on these recreational users; and 2) research should be aimed at finding therapies that can restore inhibitory control/frontal functioning and improve stress resiliency in addicts.
- Intravenous administration of cannabis and lethal anaphylaxis. [Journal Article]
- MSMed Sci Law 2017; 57(2):91-94
- Cannabis allergy appears to be increasing. A 33-year-old woman is reported who collapsed and died shortly after injecting herself with a cannabis solution prepared by pouring boiling water onto plant...
Cannabis allergy appears to be increasing. A 33-year-old woman is reported who collapsed and died shortly after injecting herself with a cannabis solution prepared by pouring boiling water onto plant material. There were no significant findings at autopsy, except for a single recent venepuncture wound in the left cubital fossa. Toxicological examination of the blood revealed low levels of methylamphetamine and amphetamine with tetrahydrocannabinol (Δ(9)-THC) and 11-nor-9-carboxy-Δ(9)-THC, and no opiates. The syringe used by the decedent contained Δ(9)-THC. Serum tryptase levels were markedly elevated (>200 µg/L; N < 12 µg/L). This finding coupled with the sudden collapse after injecting an aqueous extract of cannabis indicated a likely anaphylactic or anaphylactoid reaction to the extract. Cannabis allergy may occur following handling, inhalation, swallowing or injecting Cannabis sativa plants or their products. The possibility of an allergic reaction should therefore be considered at autopsy in deaths where there has been recent contact with cannabis.
- Amphetamine-Type-Stimulants (ATS) Use and Homosexuality-Related Enacted Stigma Are Associated With Depression Among Men Who Have Sex With Men (MSM) in Two Major Cities in Vietnam in 2014. [Journal Article]
- SUSubst Use Misuse 2017 Apr 24; :1-9
- CONCLUSIONS: We found a moderate prevalence of depression among sampled MSM, which was associated with ATS use and enacted homosexuality-related stigma. We recommend integrating assessment and interventions regarding depression and methamphetamine use into gay-friendly, culturally adapted holistic HIV prevention for MSM in Vietnam.
- Quantification of Methamphetamine in Mouse Thighbones Buried in Soil. [Journal Article]
- JFJ Forensic Sci 2017 Apr 23
- Bone samples are used for analysis of drugs in decomposed or skeletonized bodies. Toxicological analyses of buried bones are important for determining the causes and circumstances of death. In this s...
Bone samples are used for analysis of drugs in decomposed or skeletonized bodies. Toxicological analyses of buried bones are important for determining the causes and circumstances of death. In this study, methamphetamine and amphetamine concentrations in heart blood, thigh muscles, and thighbones were analyzed using solid-phase extraction with liquid chromatography-tandem mass spectrometry. Methamphetamine concentrations in heart blood, thigh muscle, and thighbone ranged from 0.041 to 0.873 μg/mL, 0.649 to 2.623 μg/g, and 56.543 to 643.371 μg/g, respectively. Thighbone concentrations were significantly higher than those in heart blood or thigh muscles were. Methamphetamine concentrations in buried thighbone (4.010-45.785 μg/g) were significantly lower than those of unburied thighbones were (56.543-643.371 μg/g). Methamphetamine and amphetamine were detected in thighbones buried for 7-180 days. These findings indicate that the methamphetamine concentrations in bone are higher and decrease after burial in soil.
- Brain lipidomic changes after morphine, cocaine and amphetamine administration - DESI - MS imaging study. [Journal Article]
- BBBiochim Biophys Acta 2017 Apr 18
- Drug addiction is a complex disorder, evoking significant changes in the proteome of the central nervous system. To check if there are also changes in the lipidomic profiles we used desorption electr...
Drug addiction is a complex disorder, evoking significant changes in the proteome of the central nervous system. To check if there are also changes in the lipidomic profiles we used desorption electrospray-MS technique for imaging of the brain slices of rats exposed to morphine, cocaine and amphetamine. Our investigations showed alternative regulation of selected lipid's levels in the central nervous system structures, under the influence of applied drugs. Results of our investigations can show changes in the brain treated with drugs of abuse in the new light, indicating role of the lipids in the addiction development.
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- Temporal dynamics of human-excreted pollutants in wastewater treatment plant influents: Toward a better knowledge of mass load fluctuations. [Journal Article]
- STSci Total Environ 2017 Apr 20; 596-597:246-255
- The occurrence of 25 drug target residues (illicit drugs or pharmaceutically active compounds) was investigated during 85 consecutive days in the influents of a wastewater treatment plant in the Regi...
The occurrence of 25 drug target residues (illicit drugs or pharmaceutically active compounds) was investigated during 85 consecutive days in the influents of a wastewater treatment plant in the Region Centre-Val de Loire, France. This long tracking period allowed a better understanding of the patterns affecting the occurrence of this type of contaminants. Among them, 2 were never detected (i.e. heroin and amphetamine). Concerning illicit drugs two patterns were found. Cocaine and ecstasy median loads varied considerably between weekdays and weekend days (i.e. 18.3 and 35.9% respectively) whereas cannabis and heroin (based on 6-mono-acetylmorphine loads) loads were within the same order of magnitude with a significant statistical correlation with pharmaceuticals such as acetaminophen or ketoprofen. The consumption of selected drugs was back-calculated from the loads. Among illicit drugs the highest consumption was found for cannabis with a median consumption of 51mg·day(-1)·inhabitant(-1) (inh) whereas the median consumption for cocaine (based on benzoylecgonine loads) and ecstasy was 32 and 6mg·day(-1)·10(3)·inh(-1) respectively. The highest consumption values of pharmaceutically active compounds (PACs) were found for acetaminophen and acetylsalicylic acid with 108.8 and 34.1mg·day(-1)·inh(-1) respectively, in good agreement with national sales data. A statistically significant weekly pattern was found for several PACs such as metoprolol and trimethoprim, but with the opposite pattern to that of illicit drugs. The variations in daily PAC loads could provide information about the mobility of people in the catchment, especially on the basis of daily taken PACs (i.e. to treat chronicle diseases).