Varenicline decreases ethanol intake and increases dopamine release via neuronal nicotinic acetylcholine receptors in the nucleus accumbens

BACKGROUND AND PURPOSE Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α4*-containing nAChRs in the ventral tegmental area (VTA). However, presynaptic nAChRs on dopaminergic terminals in the NAc have been shown to directly modulate dopaminergic signalling independently of neuronal activity from the VTA. In this study, we determined whether nAChRs in the NAc play a role in varenicline’s effects on ethanol consumption. EXPERIMENTAL APPROACH Rats were trained to consume ethanol using the intermittent-access two-bottle choice protocol for 10 weeks. Ethanol intake was measured after varenicline or vehicle was microinfused into the NAc (core, shell or core-shell border) or the VTA (anterior or posterior). The effect of varenicline treatment on DA release in the NAc was measured using both in vivo microdialysis and in vitro fast-scan cyclic voltammetry (FSCV). KEY RESULTS Microinfusion of varenicline into the NAc core and core-shell border, but not into the NAc shell or VTA, reduced ethanol intake following long-term ethanol consumption. During microdialysis, a significant enhancement in accumbal DA release occurred following systemic administration of varenicline and FSCV showed that varenicline also altered the evoked release of DA in the NAc. CONCLUSION AND IMPLICATIONS Following long-term ethanol consumption, varenicline in the NAc reduces ethanol intake, suggesting that presynaptic nAChRs in the NAc are important for mediating varenicline’s effects on ethanol consumption.

Rapid and highly efficient growth of graphene on copper by chemical vapor deposition of ethanol

The growth of graphene by chemical vapor deposition on metal foils is a promising technique to deliver large-area films with high electron mobility. Nowadays, the chemical vapor deposition of hydrocarbons on copper is the most investigated synthesis method, although many other carbon precursors and metal substrates are used too. Among these, ethanol is a safe and inexpensive precursor that seems to offer favorable synthesis kinetics. We explored the growth of graphene on copper from ethanol, focusing on processes of short duration (up to one min). We investigated the produced films by electron microscopy, Raman and X-ray photoemission spectroscopy. A graphene film with high crystalline quality was found to cover the entire copper catalyst substrate in just 20 s, making ethanol appear as a more efficient carbon feedstock than methane and other commonly used precursors.

Inter-cycle variability of ignition delay in an ethanol fumigated common rail diesel engine

An experimental study has been performed to investigate the ignition delay of a modern heavy-duty common-rail diesel engine run with fumigated ethanol substitutions up to 40% on an energy basis. The ignition delay was determined through the use of statistical modelling in a Bayesian framework this framework allows for the accurate determination of the start of combustion from single consecutive cycles and does not require any differentiation of the in-cylinder pressure signal. At full load the ignition delay has been shown to decrease with increasing ethanol substitutions and evidence of combustion with high ethanol substitutions prior to diesel injection have also been shown experimentally and by modelling. Whereas, at half load increasing ethanol substitutions have increased the ignition delay. A threshold absolute air to fuel ratio (mole basis) of above ~110 for consistent operation has been determined from the inter-cycle variability of the ignition delay, a result that agrees well with previous research of other in-cylinder parameters and further highlights the correlation between the air to fuel ratio and inter-cycle variability. Numerical modelling to investigate the sensitivity of ethanol combustion has also been performed. It has been shown that ethanol combustion is sensitive to the initial air temperature around the feasible operating conditions of the engine. Moreover, a negative temperature coefficient region of approximately 900{1050 K (the approximate temperature at fuel injection) has been shown with for n-heptane and n-heptane/ethanol blends in the numerical modelling. A consequence of this is that the dominate effect influencing the ignition delay under increasing ethanol substitutions may rather be from an increase in chemical reactions and not from in-cylinder temperature. Further investigation revealed that the chemical reactions at low ethanol substitutions are different compared to the high (> 20%) ethanol substitutions.

Anodized nanoporous WO3 Schottky contact structure for hydrogen and ethanol sensing

This paper reports the development of nanoporous tungsten trioxide (WO3) Schottky diode-based gas sensors. Nanoporous WO3 films were prepared by anodic oxidation of tungsten foil in ethylene glycol mixed with ammonium fluoride and a small amount of water. Anodization resulted in highly ordered WO3 films with a large surface-to-volume ratio. Utilizing these nanoporous structures, Schottky diode-based gas sensors were developed by depositing a platinum (Pt) catalytic contact and tested towards hydrogen gas and ethanol vapour. Analysis of the current–voltage characteristics and dynamic responses of the sensors indicated that these devices exhibited a larger voltage shift in the presence of hydrogen gas compared to ethanol vapour at an optimum operating temperature of 200 °C. The gas sensing mechanism was discussed, associating the response to the intercalating H+ species that are generated as a result of hydrogen and ethanol molecule breakdowns onto the Pt/WO3 contact and their spill over into nanoporous WO3.

Investigation of lignin biosynthesis in sugarcane for improved lignocellulosic ethanol production

As oil use increases at a rate unsustainable for the environment and unmatchable by current levels of oil production, a major shift towards renewable energy is necessary. By expanding the current knowledge of lignin biosynthesis and its manipulation in sugarcane, this PhD contributes to the production of economically viable second generation bioethanol, a fuel produced from plant biomass. The findings of this thesis contribute to the limited knowledge of lignin biosynthesis and deposition in sugarcane, and the application of biotechnology to produce sugarcane, and the resulting bagasse, with a modified cell wall. Reducing or modifying the lignin content in the cell wall of bagasse can reduce production costs and increase yields of bioethanol. This makes bioethanol more economically competitive with oil as an alternative energy source. A move to using bioethanol over fossil based transport fuels will have global economic and environmental benefits.

Fast growth of polycrystalline graphene by chemical vapor deposition of ethanol on copper

High conductive graphene films can be grown on metal foils by chemical vapor deposition (CVD). We here analyzed the use of ethanol, an economic precursor, which results also safer than commonly-used methane. A comprehensive range of process parameters were explored in order to obtain graphene films with optimal characteristics in view of their use in optoelectronics and photovoltaics. Commercially-available and electro-polished copper foils were used as substrates. By finely tuning the CVD conditions, we obtained few-layer (2-4) graphene films with good conductivity (-500 Ohm/sq) and optical transmittance around 92-94% at 550 nm on unpolished copper foils. The growth on electro-polished copper provides instead predominantly mono-layer films with lower conductivity (>1000 Ohm/sq) and with a transmittance of 97.4% at 550 nm. As for the device properties, graphene with optimal properties as transparent conductive film were produced by CVD on standard copper with specific process conditions.

Hydrothermal liquefaction of bagasse using ethanol and black liquor as solvents

The objective of this study was to examine the hydrothermal liquefaction of sugarcane bagasse using ethanol and black liquor (BL) in a pilot scale. Combinations of co-solvents (ethanol/ water, ethanol/BL) were studied at various concentrations and reaction conditions. The maximum oil yield of 61% was achieved with a reaction temperature of 300 °C for 30 min and using pure BL as a solvent, while the highest higher heating value (HHV) was obtained from a 50:50 ethanol-BL mixture. The oils contained alcohols, esters, phenolic compounds, aromatics, and heterocyclics. The O/C and H/C ratios of the oil were comparable with traditional biodiesel and commercial diesel. Although this study showed there are some improvements to be made to improve the chemical composition, the approach has potential for large-scale production of a substitute for fossil-fuel-based diesel.

Solubility of ibuprofen in aqueous ethanol at low ethanol contents

The solubility of ibuprofen was measured in water (W) - ethanol (E) mixtures from 0 to 50% w/w ethanol at 10, 25 and 40 °C by the dissolution method using UV spectrophotometry to determine the ibuprofen concentrations. The UV calibration for ibuprofen in different water - ethanol mixtures showed Beer - Lambert linearity, however the slopes differed, which indicated the structure of the drug is influenced by the solvent system i.e. the water - ethanol ratio. The ibuprofen solubility in water (zero ethanol) is low (~ 50 ppm) but increases near exponentially with increasing ethanol content. At 40 °C, there is phase separation between 34% and 63% w/w E/(E+W). The solubility data will be used to select precipitation crystallizer conditions to directly produce free flowing ibuprofen particles (<5 m) for developing a dry powder inhaler (DPI) formulation for lung delivery.

The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice

Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence. Therefore, we used a model of binge-ethanol consumption (drinking-in-the-dark) in mice to test the effects of compounds known to modify the activity of neurotransmitters implicated in alcohol addiction. From this, we have identified the FDA-approved antihypertensive drug pindolol, as a potential candidate for the management of AUDs. We show that the efficacy of pindolol to reduce ethanol consumption is enhanced following long-term (12-weeks) binge-ethanol intake, compared to short-term (4-weeks) intake. Furthermore, pindolol had no effect on locomotor activity or consumption of the natural reward sucrose. Because pindolol acts as a dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist, we examined its effect on spontaneous synaptic activity in the basolateral amygdala (BLA), a brain region densely innervated by serotonin- and norepinephrine-containing fibres. Pindolol increased spontaneous excitatory post-synaptic current frequency in BLA principal neurons from long-term ethanol consuming mice but not naïve mice. Additionally, this effect was blocked by the 5-HT1A/1B receptor antagonist methiothepin, suggesting that altered serotonergic activity in the BLA may contribute to the efficacy of pindolol to reduce ethanol intake following long-term exposure. Although further mechanistic investigations are required, this study demonstrates the potential of pindolol as a new treatment option for AUDs that can be fast-tracked into human clinical studies.

The doctrinal method: Incorporating interdisciplinary methods in reforming the law

The doctrinal methodology is in a period of change and transition. Realising that the scope of the doctrinal method is too constricting, academic lawyers are becoming eclectic in their use of research method. In this transitional time, legal scholars are increasingly infusing evidence (and methods) from other disciplines into their reasoning to bolster their reform recommendations. This article considers three examples of the interplay of the discipline of law with other disciplines in the pursuit of law reform. Firstly the article reviews studies on the extent of methodologies and reformist frameworks in PhD research in Australia. Secondly it analyses a ‘snapshot’ of recently published Australian journal articles on criminal law reform. Thirdly, it focuses on the law reform commissions, those independent government committees that play such an important role in law reform in common law jurisdictions. This examination demonstrates that while the doctrinal core of legal scholarship remains intact, legal scholars are endeavouring to accommodate statistics, comparative perspectives, social science evidence and methods, and theoretical analysis, within the legal research framework, in order to provide additional ballast to the recommendations for reform.