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It said 1kg 2. A short state television report showed the men in handcuffs and said the main suspect was arrested 17 times before. The judiciary said the Supreme Court confirmed their death sentences but did not elaborate on their trials. Foreign-based human rights organisations identified the two other executed men as Abdolhossein Emami Moghadam and Babak Aghaei. They said the men were hanged at Ghezel Hesar prison in Karaj despite pleas for clemency by family members who had gathered in front of the jail. They also said four more unnamed inmates were executed early Wednesday at Rajaei Shahr prison in Karaj, but Iranian authorities did not confirm this. It said the individual led three international groups that smuggled narcotics to several European nations, including the Netherlands, and authorities seized kg 1, pounds of heroin from him. A UN statement said more than people have been executed in but the actual number could be higher. At the current rate, executions this year would be far higher than the registered last year and could be the highest since when death sentences were carried out, the UN said. Iran executes more people annually than any other country except China, according to human rights organisations, including Amnesty International. They were accused of burning Qurans and running online groups that insulted the prophets of Islam. Video Duration 01 minutes 19 seconds By Maziar Motamedi. Published On 10 May 10 May Sponsored Content.
For accounts of other cases in the Global South, see James Mills, 'Decolonising Drugs in Asia: the case of cocaine in colonial India', Third World Quarterly
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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. A meta-analysis across both samples confirmed that CAMK2A rs TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Cocaine is the second most prevalent illegal drug in the United States and Europe after Cannabis, with a lifetime prevalence among young adults of 6. This action is known as autophosphorylation. It depends on a phosphorylation at the Thr site. The experiment involved four phases; habituation trial one session , conditioning trials 14 sessions and preference tests four sessions. Trials were performed once daily. Conditioning trials d, d and d : Mice were conditioned using a counterbalanced design. All animals received seven pairings with saline and seven pairings with cocaine in total. Preference tests d5, d10, d19 and d26 : Preference tests were performed after one, three and seven conditioning trials. A preference score was calculated from log-transformed values to normalize skewed data. Cocaine- and saline-induced locomotor activity and their sensitization were automatically scored as locomotor activity in the conditioning and pseudo-conditioning compartment after the first and seventh treatment, respectively. Cocaine- and saline-conditioned activity was automatically scored as the locomotor activity in the conditioning and pseudo-conditioning compartment, respectively, during undrugged testing during baseline and all subsequent test trials. Mice were deeply anesthetized and two guide cannulas were aimed at the prefrontal cortex PFC and the NAcc. Thereafter, mice were culled under isoflurane narcosis and transcardially perfused. Brains were taken and c-Fos activation was measured in the NAcc for details: see Supplementary Information. All controls with mean age of The characteristics of this sample were detailed previously elsewhere. Accordingly, higher the Kt, faster the transition to severe cocaine consumption was made. To replicate the gene effect found in this discovery sample, we analyzed three SNPs showing the strongest association effect sizes Supplementary Table 1 in a second and independent sample of regular cocaine users from Switzerland. PCR was performed using For experiment-specific details see Supplementary Information. The software SPSS In Ht mice, the DA response was completely absent Figure 3a. Extracellular levels of c dopamine, and d serotonin in the prefrontal cortex after acute cocaine treatment. Cocaine induces neuronal activation in the NAcc, which is the base for long-term cellular, morphological and drug use-related behavior and plasticity. While no functional gene mutation affecting the autophosphorylation site in humans is known, there are SNPs in the CAMK2A gene that may affect general activity and indirectly autophosphorylation. Kt is an index for the time to establish severe cocaine consumption from initial exposure to present day. These findings suggest a functional effect of genetic mutations in the CAMK2A gene on how fast humans develop cocaine dependence once consumption has begun, but not on whether they become cocaine users per se. At the same time it attenuated the cocaine-induced DA and 5-HT increase in both brain regions. NA responses were not affected. In the NAcc, this led to a reduced cellular activation as determined by c-Fos activity. While CPP reflects the rewarding properties of a drug, it can be derived from a number of different behavioral processes. The DA system is critical for the establishment of the acute reinforcing effects of cocaine. Neuroadaptive processes initiated by drugs of abuse are sensitive to the rate of drug administration. Previous work by Sora et al. However, basal 5-HT levels were significantly enhanced in these animals before treatment. In addition, we cannot rule out alterations in reuptake mechanisms and metabolic enzymes as a result of this mutation, or indeed cocaine administration itself, as having a crucial impact on extracellular transmitter levels seen in the present study. Cocaine effects on NAcc synaptic plasticity appeared to be under control of CaMKII in the ventral tegmental area, 19 which may, as the present study suggests, be transmitted to the NAcc by activity modulated dopaminergic projections. A crucial indicator of neuronal activation after a drug challenge is the immediate early gene c-Fos, 61 which becomes activated in the NAcc and other brain areas after acute cocaine administration by a DA and 5-HT dependent mechanism. These findings suggest that polymorphisms in the CAMK2A gene may contribute to the speed of acquiring a severe level of regular cocaine use once consumption has commenced. Although there was a genetic overlap, that is, jointly associated gene polymorphisms, in the associations between alcohol addiction and learning and memory, 9 , 25 no such overlap was found with the speed to establish severe cocaine use, which might suggest different mechanisms. Publications Office of the European Union: Luxembourg, Summary of National Findings. Add Behav ; 39 : — Article Google Scholar. Mental disorders as risk factors for later substance dependence: estimates of optimal prevention and treatment benefits. Psychol Med ; 39 : — From first drug use to drug dependence; developmental periods of risk for dependence upon marijuana, cocaine, and alcohol. Neuropsychopharmacology ; 26 : — Drugs as instruments: a new framework for non-addictive psychoactive drug use. Behav Brain Sci ; 34 : — Hyman SE. Addiction: a disease of learning and memory. Am J Psychiatry ; : — CaMKII regulation in information processing and storage. Trends Neurosci ; 35 : — CAMK2A polymorphisms predict working memory performance in humans. Mol Psychiatry a; 18 : — Giese KP, Mizuno K. The roles of protein kinases in learning and memory. Learn Mem ; 20 : — Calcium-mediated second messengers modulate the expression of behavioral sensitization to cocaine. J Pharmacol Exp Ther ; : — Genes and common pathways underlying drug addiction. PLoS Comput Biol ; 4 : e2. J Neurosci ; 33 : — Acute cocaine increases phosphorylation of CaMKII and GluA1 in the dorsolateral striatum of drug naive rats, but not cocaine-experienced rats. Neurosci Lett ; : 71— Chronic cocaine-induced H3 acetylation and transcriptional activation of CaMKIIalpha in the nucleus accumbens is critical for motivation for drug reinforcement. Neuropsychopharmacology ; 35 : — CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in cocaine seeking. Nat Neurosci ; 11 : — J Neurosci ; 31 : — CaMKII activity in the ventral tegmental area gates cocaine-induced synaptic plasticity in the nucleus accumbens. Neuropsychopharmacology ; 39 : — Science ; : — Nat Neurosci ; 8 : — Neuropharmacology ; 61 : — Trends Neurosci ; 29 : — Behav Brain Res b; : 72— Neuropsychopharmacology c; 38 : — Log transformation: application and interpretation in biomedical research. Stat Med ; 32 : — The mouse brain in stereotaxic coordinates. Google Scholar. RASGRF2 regulates alcohol-induced reinforcement by influencing mesolimbic dopamine neuron activity and dopamine release. Concurrent crack and powder cocaine users from Sao Paulo: do they represent a different group?. BMC Public Health ; 6 : Dunn J, Laranjeira R. The development of a structured interview to evaluate cocaine use and risk behaviour. Rev Bras Psiquiatr ; 22 : 11— PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet ; 81 : — The structure of haplotype blocks in the human genome. Cognitive dysfunctions in recreational and dependent cocaine users: role of attention-deficit hyperactivity disorder, craving and early age at onset. Br J Psychiatry ; : 35— Altered social and non-social decision-making in recreational and dependent cocaine users. Psychol Med ; 44 : — Impaired emotional empathy and related social network deficits in cocaine users. Addict Biol ; 19 : — Whitlock MC. J Evol Biol ; 18 : — Hedges LV Olkin I. Statistical methods for meta-analysis. Microdialysis in rodents. Curr Protoc Neurosci ; Chapter 7 : Unit 7. Homer2 is necessary for EtOH-induced neuroplasticity. J Neurosci ; 25 : — Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Role of medial prefrontal, entorhinal, and occipital 5-HT in cocaine-induced place preference and hyperlocomotion: evidence for multiple dissociations. Psychopharmacology Berl ; : — Robinson TE, Kolb B. Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology ; 47 : 33— Neuroplasticity in the mesolimbic dopamine system and cocaine addiction. Br J Pharmacol ; : — J Neurosci ; 32 : — What's conditioned in conditioned place preference?. Trends Pharmacol Sci ; 34 : — Int J Comp Psychol ; 14 : — Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies. Behav Brain Res ; : — Why does the rapid delivery of drugs to the brain promote addiction?. Trends Pharmacol Sci ; 26 : 82— Crack cocaine and cocaine hydrochloride. Are the differences myth or reality?. JAMA ; : — Nature ; : — J Neurosci ; 22 : — Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels. Nat Cell Biol ; 2 : — Griffith LC, Schulman H. J Biol Chem ; : — Brain Res ; : 1— Cocaine reward models: conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. Double dissociating effects of sensory stimulation and cocaine on serotonin activity in the occipital and temporal cortices. Neuropharmacology a; 52 : — Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors. Prog Neurobiol b; 81 : — Dissociating effects of cocaine and d-amphetamine on dopamine and serotonin in the perirhinal, entorhinal, and prefrontal cortex of freely moving rats. Phosphorylation and activation of tryptophan hydroxylase 2: identification of serine as the substrate site for calcium, calmodulin-dependent protein kinase II. J Neurochem ; : — Expression of the immediate early gene c-fos in basal ganglia: induction by dopaminergic drugs. Can J Neurol Sci ; 18 : — Activation of transcription factor genes in striatum by cocaine—role of both serotonin and dopamine systems. J Pharmacol Exp Therap ; : — CAS Google Scholar. Download references. You can also search for this author in PubMed Google Scholar. Supplementary Information accompanies the paper on the Translational Psychiatry website. Reprints and permissions. Easton, A. Transl Psychiatry 4 , e Download citation. Received : 02 May Revised : 18 July Accepted : 21 August Published : 07 October Issue Date : October Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content Thank you for visiting nature. Download PDF. Subjects Addiction Molecular neuroscience. Abstract Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. GluN2B inhibition confers resilience against long-term cocaine-induced neurocognitive sequelae Article 02 September Introduction Cocaine is the second most prevalent illegal drug in the United States and Europe after Cannabis, with a lifetime prevalence among young adults of 6. Conditioned hyperactivity Cocaine- and saline-conditioned activity was automatically scored as the locomotor activity in the conditioning and pseudo-conditioning compartment, respectively, during undrugged testing during baseline and all subsequent test trials. In vivo microdialysis Mice were deeply anesthetized and two guide cannulas were aimed at the prefrontal cortex PFC and the NAcc. Figure 1. Full size image. Figure 2. Figure 3. Figure 4. Figure 5. View author publications. Ethics declarations Competing interests The authors declare no conflict of interest. Additional information Supplementary Information accompanies the paper on the Translational Psychiatry website. Supplementary information. Supplementary Information DOC kb. About this article. Cite this article Easton, A. Copy to clipboard. Search Search articles by subject, keyword or author. Show results from All journals This journal. Advanced search.
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