The Validity of the Environmental Kuznets Curve for the European Union

This research empirically explores the validity of the environmental Kuznets curve (EKC) for the European Union. Data for CO2 emission per capita, GDP per capita, population density, and fossil fuel consumption percentage was gathered for the 28 countries within the European Union for years 1990-2010 and regression analysis was conducted in order to see if the EKC relationship held true. However, under this analysis, that result is inconclusive. As GDP per capita increases, CO2 increases to a certain point and then, instead of having a negative relationship, it continues to increase but at a lesser rate. The coefficients of the natural log of GDP and the natural log of GDP squared were both positive. In fact, the coefficient does not turn negative until the cubed root of the variable was taken. In order to explore this outcome, we separated the EU into two groups: first 13 members and newer members. We ran the same analysis for both groups and found that the EKC relationship was true for the first 13 members and was not true for the new members. This shows that the first 13 members are more developed and further along the left side of the Kuznets curve than the newer members, and the newer member countries have skewed the overall outcome for the EU causing them to sit further left upon the EKC

Identifying the role of pre-and postsynaptic GABAB receptors in behavior.

Although many reviews exist characterizing the molecular differences of GABAB receptor isoforms, there is no current review of the in vivo effects of these isoforms. The current review focuses on whether the GABAB1a and GABAB1b isoforms contribute differentially to behaviors in isoform knockout mice. The roles of these receptors have primarily been characterized in cognitive, anxiety, and depressive phenotypes. Currently, the field supports a role of GABAB1a in memory maintenance and protection against an anhedonic phenotype, whereas GABAB1b appears to be involved in memory formation and a susceptibility to developing an anhedonic phenotype. Although GABAB receptors have been strongly implicated in drug abuse phenotypes, no isoform-specific work has been done in this field. Future directions include developing site-specific isoform knockdown to identify the role of different brain regions in behavior, as well as identifying how these isoforms are involved in development of behavioral phenotypes

Intra-nucleus accumbens shell injections of R(+)- and S(-)-baclofen bidirectionally alter binge-like ethanol, but not saccharin, intake in C57Bl/6J mice

The GABAB agonist baclofen has been widely researched clinically and preclinically as a treatment of alcohol use disorders (AUDs). However, the efficacy of baclofen remains uncertain. The clinically used racemic compound can be separated into separate enantiomers. These enantiomers have produced different profiles in behavioral assays, with the S- compound often being ineffective compared to the R- compound, or the S- compound antagonizing the effects of the R- compound. We have previously demonstrated that the R(+)-baclofen enantiomer decreases binge-like ethanol intake in the Drinking-in-the-Dark (DID) paradigm, whereas the S(-)-baclofen enantiomer increases ethanol intake. One area implicated in drug abuse is the nucleus accumbens shell (NACsh).The current study sought to define the role of the NACsh in the enantioselective effects of baclofen on binge-like ethanol consumption by directly microinjecting each enantiomer into the structure. Following bilateral cannulation of the NACsh, C57Bl/6J mice were given 5 days of access to ethanol or saccharin for 2h, 3h into the dark cycle. On Day 5 mice were given an injection of aCSF, 0.02 R(+)-, 0.04R(+)-, 0.08 S(-)-, or 0.16 S(-)-baclofen (μg/side dissolved in 200nl of aCSF). It was found that the R(+)-baclofen dose-dependently decreased ethanol consumption, whereas the high S(-)-baclofen dose increased ethanol consumption, compared to the aCSF group. Saccharin consumption was not affected. These results further confirm that GABAB receptors and the NACsh shell are integral in mediating ethanol intake. They also demonstrate that baclofen displays bidirectional, enantioselective effects which are important when considering therapeutic uses of the drug

Bidirectional enantioselective effects of the GABAB receptor agonist baclofen in two mouse models of excessive ethanol consumption

The GABAB receptor agonist baclofen has been studied extensively in preclinical models of alcohol-use disorders, yet results on its efficacy have been uncertain. Racemic baclofen, which is used clinically, can be broken down into separate enantiomers of the drug. Baclofen has been shown to produce enantioselective effects in behavioral assays, including those modeling reflexive and sexual behavior. The current studies sought to characterize the enantioselective effects of baclofen in two separate models of ethanol consumption. The first was a Drinking-in-the-Dark procedure that provides "binge-like" ethanol access to mice by restricting access to a 2-h period, 3 h into the dark cycle. The second was a two-bottle choice procedure that utilized selectively bred High Alcohol Preferring 1 (HAP1) mice to model chronic ethanol access. HAP1 mice are selectively bred to consume pharmacologically relevant amounts of ethanol in a 24-h two-bottle choice paradigm. The results showed that baclofen yields enantioselective effects on ethanol intake in both models, and that these effects are bidirectional. Total ethanol intake was decreased by R(+)-baclofen, while total intake was increased by S(-)-baclofen in the binge-like and chronic drinking models. Whereas overall binge-like saccharin intake was significantly reduced by R(+)-baclofen, chronic intake was not significantly altered. S(-)-baclofen did not significantly alter saccharin intake. Neither enantiomer significantly affected locomotion during binge-like reinforcer consumption. Collectively, these results demonstrate that baclofen produces enantioselective effects on ethanol consumption. More importantly, the modulation of consumption is bidirectional. The opposing enantioselective effects may explain some of the variance seen in published baclofen literature

Development of Cross-Tolerance Between Ethanol and Baclofen in C57Bl/6J Mice

poster abstractAlcohol is one of the most commonly used drugs of abuse. One criteria of alcohol abuse is the development of tolerance, meaning that more of the substance has to be ingested to produce the same pharmacological or behavioral effects. The phenomenon of cross-tolerance is when use of one substance leads to tolerance to an unused substance. Ethanol has also been shown to produce cross-tolerance to other drugs, such as benzodiazepines. The purpose of the current study was to investigate whether prior binge-like ethanol exposure in C57Bl/6J (B6) mice would produce a cross-tolerance to the locomotor sedative effects of the GABAB agonist R(+)-baclofen. We exposed 32 B6 male mice to a limited-access binge-like drinking procedure. Mice received daily access to either 0.2% saccharin or 20% ethanol for 2 hours, 3 hours into the dark cycle each day. There were four groups; 5 days of saccharin or ethanol access, and 10 days of saccharin or ethanol access. Baseline locomotor recordings were taken before ethanol drinking using Versamax activity monitors. Twenty-two hours following the last day of binge-like ethanol access, all animals received a 10mg/kg injection of R(+)-baclofen and Versamax activity was recorded for 1 hour. Sedation scores were calculated by subtracting the challenge day locomotor scores from the baseline locomotor scores. There was no effect of length of exposure (5 versus 10 days) or fluid type (ethanol versus saccharin) on total sedation scores (p<.05). A Length of Exposure*Fluid Type*Time-Bin ANOVA looking at sedation scores in 5 minute bins revealed a trend towards an omnibus interaction, but it did not reach significance (p=0.64). There was a main effect of time, with sedation scores being lower immediately following the injection (9<.05). These results indicate that ethanol does not produce a locomotors cross-tolerance to R(+)-baclofen

Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC)

Cannabis use is linked to positive and negative outcomes. Identifying genetic targets of susceptibility to the negative effects of cannabinoid use is of growing importance. The current study sought to complete short-term selective breeding for adolescent sensitivity and resistance to the locomotor effects of a single 10 mg/kg THC dose in the open field. Selection for THC-locomotor sensitivity was moderately heritable, with the greatest estimates of heritability seen in females from the F2 to S3 generations. Selection for locomotor sensitivity also resulted in increased anxiety-like activity in the open field. These results are the first to indicate that adolescent THC-locomotor sensitivity can be influenced via selective breeding. Development of lines with a genetic predisposition for THC-sensitivity or resistance to locomotor effects allow for investigation of risk factors, differences in consequences of THC use, identification of correlated behavioral responses, and detection of genetic targets that may contribute to heightened cannabinoid sensitivity

Issues in the reporting of epidemiological studies: a survey of recent practice.

OBJECTIVES: To review current practice in the analysis and reporting of epidemiological research and to identify limitations. DESIGN: Examination of articles published in January 2001 that investigated associations between risk factors/exposure variables and disease events/measures in individuals. SETTING: Eligible English language journals including all major epidemiological journals, all major general medical journals, and the two leading journals in cardiovascular disease and cancer. MAIN OUTCOME MEASURE: Each article was evaluated with a standard proforma. RESULTS: We found 73 articles in observational epidemiology; most were either cohort or case-control studies. Most studies looked at cancer and cardiovascular disease, even after we excluded specialty journals. Quantitative exposure variables predominated, which were mostly analysed as ordered categories but with little consistency or explanation regarding choice of categories. Sample selection, participant refusal, and data quality received insufficient attention in many articles. Statistical analyses commonly used odds ratios (38 articles) and hazard/rate ratios (23), with some inconsistent use of terminology. Confidence intervals were reported in most studies (68), though use of P values was less common (38). Few articles explained their choice of confounding variables; many performed subgroup analyses claiming an effect modifier, though interaction tests were rare. Several investigated multiple associations between exposure and outcome, increasing the likelihood of false positive claims. There was evidence of publication bias. CONCLUSIONS: This survey raises concerns regarding inadequacies in the analysis and reporting of epidemiological publications in mainstream journals

Concomitant Caffeine Increases Binge Consumption of Ethanol in Adolescent and Adult Mice, But Produces Additive Motor Stimulation Only in Adolescent Animals

BACKGROUND: Binge co-consumption of highly caffeinated energy drinks with alcohol (ethanol [EtOH]) has become a common practice among adolescents/young adults and has been associated with an increased incidence of hazardous behaviors. Animal models are critical in advancing our understanding the neurobehavioral consequences of this form of binge drinking. Surprisingly, virtually no work has explored caffeine and EtOH co-consumption or its long-term consequences in adolescent animals. The primary objective of the current study was to extend a previously established mouse model of voluntary binge caffeine and EtOH co-consumption to explore adolescent consumption and responses compared to adults. METHODS: Adolescent and adult male C57BL/6J mice had daily limited access to caffeine (0.03% w/v), EtOH (20% v/v), a combined EtOH/caffeine solution, or water for 14 days via the binge-like drinking paradigm, drinking-in-the-dark (DID). Home cage locomotor activity was measured during DID in a subset of mice. Following DID, all mice rested for 18 days so that adolescents reached adulthood, whereupon all mice underwent 7 days of continuous access 2-bottle choice drinking for 10% (v/v) EtOH or water. RESULTS: Co-consumption with caffeine significantly increased EtOH intake and resultant blood ethanol concentrations in both adolescent and adult mice. In addition, adolescent mice exhibited a uniquely robust locomotor stimulant response to caffeine and EtOH co-consumption. Later EtOH intake and preference was not influenced, however, by prior fluid consumption history via DID. CONCLUSIONS: Together with findings from the human literature, our results suggest that caffeine co-consumption may positively influence binge alcohol consumption in adolescents/young adults. Importantly, this age group may be particularly sensitive to the additive stimulant effects of caffeinated alcohol consumption, an effect which may be related to the high incidence of associated negative outcomes in this population. These observations are particularly concerning considering the heightened plasticity of the adolescent brain