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Altered dopamine (DA) transporter densities have been implicated in mechanisms of vulnerability and relapse in human alcoholics. The regional distribution and density of the DA transporter was studied in alcohol-preferring vervet monkeys to investigate baseline status and regulation of the DA transporter at different stages of chronic alcohol drinking. Combined ligand binding and in vitro autoradiography of the cocaine congener [125I]RTI-55 (beta-CIT) demonstrated a significant increase in DA transporter densities in abstinent alcohol-preferring monkeys over those in alcohol-avoiding monkeys. Chronic alcohol consumption down-regulated DA transporter densities, and this effect was reversed by acute withdrawal. These results demonstrate that the DA transporter is regulated by alcohol exposure and suggest that increased DA transporter densities may be a phenotypic marker of alcohol preference in vulnerable monkeys.

Breathing and oxygenation were monitored in 78 asymptomatic volunteers on two successive nights of sleep. Four groups of subjects were recruited: 20 young men, 20 young women, 20 men older than 40 years, and 18 postmenopausal women. In random order, subjects ingested either 2 ml/kg (body weight) of 100-proof vodka in orange juice or a similar amount of water in orange juice before bedtime. Alcohol ingestion shortened sleep in the older men and in the postmenopausal women. No effect of alcohol ingestion on breathing or oxygenation during sleep was seen in any group of women. In men, alcohol ingestion increased the numbers of desaturation episodes and caused more severe oxygen desaturation during sleep. The effect of alcohol ingestion on breathing and oxygenation during the sleep of asymptomatic volunteers appears to be limited to men.

Previous studies reveal that the primary distribution of the current density is sharply enhanced at the edge of a disk electrode submerged into a semi-infinite space of conductive solution. The current enhancement will cause the double layer capacitance at the periphery of the electrode to be charged much faster compared to the center, and can also lead to severe corrosion at the edge. While several studies focused on the geometric design of the electrode to reduce this enhancement, we explore the feasibility of achieving similar effect by shaping the edges of the current input. The simulation uses finite element analysis software to solve the system of partial differential equations and results show that the edge enhancement could be greatly reduced without significantly changing the input efficacy of current and/or charge.

Background:  We previously found that activation of the glial cell line‐derived neurotrophic factor (GDNF) pathway in the ventral tegmental area (VTA) reduces ethanol‐drinking behaviors. In this study, we set out to assess the contribution of endogenous GDNF or its receptor GFRα1 to the regulation of ethanol‐related behaviors.Methods:  GDNF and GFRα1 heterozygote mice (HET) and their wild‐type littermate controls (WT) were used for the studies. Ethanol‐induced hyperlocomotion, sensitization, and conditioned place preference (CPP), as well as ethanol consumption before and after a period of abstinence were evaluated. Blood ethanol concentration (BEC) was also measured.Results:  We observed no differences between the GDNF HET and WT mice in the level of locomotor activity or in sensitization to ethanol‐induced hyperlocomotion after systemic injection of a nonhypnotic dose of ethanol and in BEC. However, GDNF and GFRα1 mice exhibited increased place preference to ethanol as compared with their WT littermates. The levels of voluntary ethanol or quinine consumption were similar in the GDNF HET and WT mice, however, a small but significant increase in saccharin intake was observed in the GDNF HET mice. No changes were detected in voluntary ethanol, saccharin or quinine consumption of GFRα1 HET mice as compared with their WT littermates. Interestingly, however, both the GDNF and GFRα1 HET mice consumed much larger quantities of ethanol after a period of abstinence from ethanol as compared with their WT littermates. Furthermore, the increase in ethanol consumption after abstinence was found to be specific for ethanol as similar levels of saccharin intake were measured in the GDNF and GFRα1 HET and WT mice after abstinence.Conclusions:  Our results suggest that endogenous GDNF negatively regulates the rewarding effect of ethanol and ethanol‐drinking behaviors after a period of abstinence.

To discuss current evidence of global climate change and its implications for allergic rhinitis and other allergic respiratory diseases.Global climate change is evidenced by increasing average earth temperature, increasing anthropogenic greenhouse gas levels, and elevated pollen levels. Pollutants of interest include carbon dioxide (CO2), ozone (O3), and nitrous oxide (NO2) because they can enhance the allergic response and lead to increased symptoms of allergic respiratory diseases. Heightened CO2 levels stimulate pollen production via photosynthesis and increased growth in multiple plant species investigated. Although worsened air quality appears to increase prevalence of allergic rhinitis, the effects of increased temperature are less certain. The findings of increased aeroallergen levels likely contribute to increases in presentation of allergic diseases, although more healthcare impact studies are necessary.Although recent literature indicates and strongly supports changes in temperature, pollution levels, and aeroallergen levels, more longitudinal epidemiologic surveillance of allergic diseases in relation to climate change as well as pathophysiologic studies on changing aeroallergen effects on allergic diseases are needed.

ABSTRACTPrenatal ethanol exposure causes a variety of cognitive deficits that have a persistent impact on quality of life, some of which may be explained by ethanol-induced alterations in interneuron function. Studies from several laboratories, including our own, have demonstrated that a single binge-like ethanol exposure during the equivalent to the third trimester of human pregnancy leads to acute apoptosis and long-term loss of interneurons in the rodent retrosplenial cortex (RSC). The RSC is interconnected with the hippocampus, thalamus, and other neocortical regions and plays distinct roles in visuospatial processing and storage, as well as retrieval of hippocampal-dependent episodic memories. Here we used slice electrophysiology to characterize the acute effects of ethanol on GABAergic neurotransmission in the RSC of neonatal mice, as well as the long-term effects of neonatal ethanol exposure on parvalbumin-interneuron mediated neurotransmission in adolescent mice. Mice were exposed to ethanol using vapor inhalation chambers. In postnatal day (P) 7 mouse pups, ethanol unexpectedly failed to potentiate GABAAreceptor-mediated synaptic transmission. Binge-like ethanol exposure of P7 mice expressing channel rhodopsin in parvalbumin-positive interneurons enhanced the peak amplitudes, asynchronous activity and total charge, while decreasing the rise-times of optically-evoked GABAAreceptor-mediated inhibitory postsynaptic currents in adolescent animals. These effects could partially explain the learning and memory deficits that have been documented in adolescent and young adult mice exposed to ethanol during the third trimester-equivalent developmental period.

TorsinA, a novel protein in which a mutation causes dominant, early onset torsion dystonia, may serve as a chaperone for misfolded proteins that require refolding or degradation. It has been hypothesized that misfolded alpha-synuclein, a protein in which two mutations cause autosomal dominantly inherited Parkinson's disease, serves as a nidus for the development of a Lewy body. We hypothesized that torsinA plays a role in the cellular processing of alpha-synuclein. We demonstrate that anti-torsin antibodies stain Lewy bodies and Lewy neurites in the substantia nigra and cortex. Using sensitive fluorescent resonance energy transfer (FRET) techniques, we find evidence of a close association between torsinA and alpha-synuclein in Lewy bodies.

Background:  A low level of response (i.e., a low LR) to alcohol is a genetically influenced phenotype that predicts later alcoholism. While the low LR reflects, at least in part, a low brain response to alcohol, the physiological underpinnings of the low LR have only recently been addressed. Methods:  Forty‐nine drinking but not yet alcoholic matched pairs of 18‐ to 25‐year‐old subjects (N = 98; 53% women) with low and high LRs as established in separate alcohol challenges were evaluated in 2 event‐related functional magnetic resonance imaging (fMRI) sessions (placebo and approximately 0.7 ml/kg of alcohol) while performing a validated stop signal task. The high and low LR groups had identical blood alcohol levels during the alcohol session. Results:  Significant high versus low LR group and LR group × condition effects were observed in blood oxygen level–dependent (BOLD) signal during error and inhibitory processing, despite similar LR group performance on the task. In most clusters with significant (corrected p < 0.05, clusters > 1,344 μl) LR group × alcohol/placebo condition interactions, the low LR group demonstrated relatively less, whereas the high LR group demonstrated more, error and inhibition‐related activation after alcohol compared with placebo. Conclusions:  This is one of the first fMRI studies to demonstrate significant differences between healthy groups with different risks of a future life‐threatening disorder. The results may suggest a brain mechanism that contributes to how a low LR might enhance the risk of future heavy drinking and alcohol dependence.