Drug-Induced Plasticity Contributing to Heightened Relapse Susceptibility: Neurochemical Changes and Augmented Reinstatement in High-Intake Rats

A key in understanding the neurobiology of addiction and developing effective pharmacotherapies is revealing drug-induced plasticity that results in heightened relapse susceptibility. Previous studies have demonstrated that increased extracellular glutamate, but not dopamine, in the nucleus accumbens core (NAcc) is necessary for cocaine-induced reinstatement. In this report, we examined whether drug-induced adaptations that are necessary to generate cocaine-induced reinstatement also determine relapse vulnerability. To do this, rats were assigned to self-administer cocaine under conditions resulting in low (2 h/d; 0.5 mg/kg/infusion, i.v.) or high (6 h/d; 1.0 mg/kg/infusion, i.v.) levels of drug intake since these manipulations produce groups of rats exhibiting differences in the magnitude of cocaine-induced reinstatement. Approximately 19 d after the last session, cocaine-induced drug seeking and extracellular levels of glutamate and dopamine in the NAcc were measured. Contrary to our hypothesis, high-intake rats exhibited a more robust cocaine-induced increase in extracellular levels of dopamine but not glutamate. Further, increased reinstatement in high-intake rats was no longer observed when the D1 receptor antagonist SCH-23390 was infused into the NAcc. The sensitized dopamine response to cocaine in high-intake rats may involve blunted cystine–glutamate exchange by system xc−. Reduced 14C-cystine uptake through system xc− was evident in NAcc tissue slices obtained from high-intake rats, and the augmented dopamine response in these rats was no longer observed when subjects received the cysteine prodrug N-acetyl cysteine. These data reveal a role for drug-induced NAcc dopamine in heightened relapse vulnerability observed in rats with a history of high levels of drug intake

Blunted Cystine–Glutamate Antiporter Function in the Nucleus Accumbens Promotes Cocaine-induced Drug Seeking

Repeated cocaine alters glutamate neurotransmission, in part, by reducing cystine–glutamate exchange via system xc−, which maintains glutamate levels and receptor stimulation in the extrasynaptic compartment. In the present study, we undertook two approaches to determine the significance of plasticity involving system xc−. First, we examined whether the cysteine prodrug N-acetylcysteine attenuates cocaine-primed reinstatement by targeting system xc−. Rats were trained to self-administer cocaine (1 mg/kg/200 μl, i.v.) under extended access conditions (6 h/day). After extinction training, cocaine (10 mg/kg, i.p.) primed reinstatement was assessed in rats pretreated with N-acetylcysteine (0–60 mg/kg, i.p.) in the presence or absence of the system xc− inhibitor (S)-4-carboxyphenylglycine (CPG; 0.5 μM; infused into the nucleus accumbens). N-acetylcysteine attenuated cocaine-primed reinstatement, and this effect was reversed by co-administration of CPG. Secondly, we examined whether reduced system xc− activity is necessary for cocaine-primed reinstatement. To do this, we administered N-acetylcysteine (0 or 90 mg/kg, i.p.) prior to 12 daily self-administration sessions (1 mg/kg/200 μl, i.v.; 6 h/day) since this procedure has previously been shown to prevent reduced activity of system xc−. On the reinstatement test day, we then acutely impaired system xc− in some of the rats by infusing CPG (0.5 μM) into the nucleus accumbens. Rats that had received N-acetylcysteine prior to daily self-administration sessions exhibited diminished cocaine-primed reinstatement; this effect was reversed by infusing the cystine–glutamate exchange inhibitor CPG into the nucleus accumbens. Collectively these data establish system xc− in the nucleus accumbens as a key mechanism contributing to cocaine-primed reinstatement

Studi Metodologis Fikih Zakat Profesi dalam Perspektif Yusuf Al-Qardhawi

The purpose of this study was to determine the method, foundation and reasoning of Yusuf al-Qardhawi's law on professional zakat. This research is a library research with data collection methods in the form of quoting, adapting and analyzing using content analysis. The results showed that according to Yusuf al-Qardhawi, ijtihad is a serious effort by exerting all abilities by those who have the authority in order to find answers to religious law through istinbât both done hourly (collective) or fardi (individual) by involving other experts . The results of the ijtihad are based on the maqâsid al-syarî‘ah using the qiyas method. On the basis of this principle Yusuf al-Qardhawi stipulates that in determining the obligatory zakat from the profession does not wait a year. The determination of the law does not stand alone, but is supported by the Qur'anic texts, hadith, and analogies. The aspect of justice in determining the obligation of professional zakat for every Muslim is because zakat is essentially worship related to property. A person who has fulfilled his requirements is required to fulfill it, not solely on the basis of his generosity, but if necessary even under pressure from the authorities

Kepribadian Tokoh dalam Novel Entrok Karya Okky Madasari

Tujuan penelitian mendeskripsikan kepribadian tokoh pada novel Entrok karya Okky Madasari di lihat dari aspek id, ego dan superego. Penelitian ini menggunakan teori psikologi sastra yang mengkaji tentang kepribadian tokoh dengan menggunakan teori Sigmund Freud yang meliputi Aspek id, ego dan superego. Metode penelitian ini adalah Metode deskriptif kualitatif. Hasil penelitian dan pembahasan menunjukan bahwa, (1) kepribadian tokoh Marni dalam novel Entrok karya Okky Madasari dilihat dari aspek id, ego dan superego. (2) kepribadian tokoh Rahayu dalam novel Entrok karya Okky Madasari dilihat dari aspek id, ego dan superego. (3) kepribadian tokoh Simbok dalam novel Entrok karya Okky Madasari dilihat dari aspek id, ego dan superego. (4) kepribadian tokoh Teja dalam novel Entrok karya Okky Madasari dilihat dari aspek id,ego dan superego

Repeated \u3cem\u3eN\u3c/em\u3e-Acetylcysteine Administration Alters Plasticity-Dependent Effects of Cocaine

Cocaine produces a persistent reduction in cystine–glutamate exchange via system xc− in the nucleus accumbens that may contribute to pathological glutamate signaling linked to addiction. System xc− influences glutamate neurotransmission by maintaining basal, extracellular glutamate in the nucleus accumbens, which, in turn, shapes synaptic activity by stimulating group II metabotropic glutamate autoreceptors. In the present study, we tested the hypothesis that a long-term reduction in system xc− activity is part of the plasticity produced by repeated cocaine that results in the establishment of compulsive drug seeking. To test this, the cysteine prodrug N-acetylcysteine was administered before daily cocaine to determine the impact of increased cystine–glutamate exchange on the development of plasticity-dependent cocaine seeking. Although N-acetylcysteine administered before cocaine did not alter the acute effects of cocaine on self-administration or locomotor activity, it prevented behaviors produced by repeated cocaine including escalation of drug intake, behavioral sensitization, and cocaine-primed reinstatement. Because sensitization or reinstatement was not evident even 2–3 weeks after the last injection of N-acetylcysteine, we examined whether N-acetylcysteine administered before daily cocaine also prevented the persistent reduction in system xc− activity produced by repeated cocaine. Interestingly, N-acetylcysteine pretreatment prevented cocaine-induced changes in [35S]cystine transport via system xc−, basal glutamate, and cocaine-evoked glutamate in the nucleus accumbens when assessed at least 3 weeks after the last N-acetylcysteine pretreatment. These findings indicate that N-acetylcysteine selectively alters plasticity-dependent behaviors and that normal system xc− activity prevents pathological changes in extracellular glutamate that may be necessary for compulsive drug seeking

Effects of cultivation year and growing location on the phenolic profile of differently coloured carrot cultivars

Carrots (Daucus carota L.) are economically and nutritionally important crops that, apart from carotenoids, contain numerous phenolic compounds which are assumed to exert health beneficial effects. The total phenolic contents of fruits and vegetables are known to depend on cultivar and growing conditions; however, studies examining the variability of a collection of carrots comprising differently coloured cultivars are rare. Therefore, the objective of the present study was to investigate the phenolic compounds of ten differently coloured carrot cultivars considering the effects of three cultivation years at two growing locations. Although total phenolic contents varied in a wide range, both purple cultivars ‘Anthonina’ and ‘Deep Purple’ significantly exceeded those of yellow, orange, red, and uncoloured cultivars (P ≤ 0.05) with amounts from 4,113 to 11,737 mg [kg dry matter (DM)]-1. In contrast to the purple roots, the other generally were characterised by far lower polyphenol contents ranging from 33 to 1,369 mg (kg DM)-1. Interestingly, the values did not considerably vary within these cultivars. In the present study, contrary to cultivar specific effects, the infl uence of growing location was found to be rather weak, supposedly due to similar climatic conditions at both locations. Similarly, variation of phenolic contents from year-to-year was less pronounced. In conclusion, the selection of breeding material was found to be of utmost importance regarding the expression of polyphenols in differently coloured carrots

Methodological Study of Juriscprudence of Professional Zakat in Yusuf al-Qardhawi's Perspective

The purpose of this study was to determine the method, foundation and reasoning of Yusuf al-Qardhawi's law on professional zakat. This research is a library research with data collection methods in the form of quoting, adapting and analyzing using content analysis. The results showed that according to Yusuf al-Qardhawi, ijtihad is a serious effort by exerting all abilities by those who have the authority in order to find answers to religious law through istinbât both done hourly (collective) or fardi (individual) by involving other experts . The results of the ijtihad are based on the maqâsid al-syarî‘ah using the qiyas method. On the basis of this principle Yusuf al-Qardhawi stipulates that in determining the obligatory zakat from the profession does not wait a year. The determination of the law does not stand alone, but is supported by the Qur'anic texts, hadith, and analogies. The aspect of justice in determining the obligation of professional zakat for every Muslim is because zakat is essentially worship related to property. A person who has fulfilled his requirements is required to fulfill it, not solely on the basis of his generosity, but if necessary even under pressure from the authorities.Tujuan penelitian ini adalah untuk mengetahui metode, landasan dan penalaran hukum Yusuf al-Qardhawi tentang zakat profesi. Penelitian ini adalah penelitian kepustakaan dengan metode pengumpulan data berupa mengutip, menyadur dan menganalisis dengan menggunakan analisis isi. Hasil penelitian menunjukkan bahwa menurut Yusuf al-Qardhawi, ijtihad merupakan upaya yang sungguh-sungguh dengan mengerahkan segala kemampuan oleh yang memiliki otoritas dalam rangka menemukan jawaban hukum agama melalui istinbât baik dilakukan secara jamâ’î (kolektif) maupun fardî (individu) dengan melibatkan pakar lain. Hasil ijtihad tersebut didasarkan kepada maqâsid al-syarî‘ah dengan menggunakan metode qiyas. Atas dasar prinsip inilah Yusuf al-Qardhawi menetapkan dalam menentukan wajib zakat hasil profesi tidak menunggu satu tahun. Penetapan hukum tersebut tidak berdiri sendiri, tetapi didukung oleh nash al-Quran, hadis, dan analogi. Aspek keadilan dalam penentuan kewajibannya zakat profesi bagi setiap muslim karena secara esensial zakat adalah ibadah yang berkaitan dengan harta benda. Seseorang yang telah memenuhi syarat-syaratnya dituntut untuk menunaikannya, bukan semata-mata atas dasar kemurahan hatinya, tetapi kalau perlu bahkan dengan tekanan penguasa

The influence of using digital diagnostic information on orthodontic treatment planning - a pilot study

The purpose of this pilot study was to assess whether orthodontic treatment planning is reproducible when carried out using digital records compared with clinical examinations or using standard records. The study also assessed patients' opinion of face-to-face consultations and potential use of teleorthodontics. The study was designed as a prospective observational cross-sectional pilot study and carried out in a UK dental teaching hospital involving 27 subjects. Four consultant Orthodontists carried out treatment planning, firstly following a clinical examination, then using standard records, and then using digital records. Each subject completed a questionnaire. Cohen's kappa coefficient and Fleiss' kappa coefficient were used to assess intra-observer reproducibility and inter-observer reproducibility of treatment planning decisions, respectively. A change in the diagnostic information format affected treatment planning reproducibility for half of the observers. Inter-observer reproducibility was greater when using hard copy records in comparison to digital records. No subjects were unsatisfied with their face-to-face consultation