AN EXAMINATION OF DEVELOPMENTAL AND SEX DIFFERENCES IN ETHANOL CONSUMPTION BY LOW ALCOHOL-CONSUMING RAT LINES

poster abstractIn the United States, alcohol use and dependence is a major health issue affecting 4-5% of the population (Hasin et al., 2007). Research indicates ad-olescents ages 12-20 drink 11% of all alcohol consumed nationally, with more than 90% consumed in the form of binge drinking (Center for Disease Control and Prevention, 2010). Similar to the human condition, adolescent rodents generally consume more ethanol than their adult counterparts. Current rat animal model studies on alcoholism remain weighted toward examining Family History Positive (FHP), selectively bred, alcohol-preferring lines. Also, research has generally been focused on ethanol consumption be-havior of male rodents. However, female rodents tend to consume more al-cohol than male rodents (e.g., Adams et al., 1991). In addition, existing re-search on adolescent vs. adult alcohol abuse using “FHP” rats is not paral-leled by research with “Family History Negative” (FHN) rats, which might re-veal factors that prevent/protect an individual from excessive ethanol intake during this crucial stage of development. The purpose of this study was to evaluate ethanol consumption by male and female FHN, selectively bred, alcohol-nonpreferring rats during adoles-cence and adulthood. Studying adolescent vs. adult behavior may reveal de-velopmentally-specific, protective factors. Also, examining male versus fe-male behavior may reveal sex-by-development factors guarding against al-cohol abuse. Animals were placed in cages and assigned to experimental conditions defined by the following independent variables: line of rodent, rodent’s sex and age of ethanol exposure. The following dependent measures were exam-ined: changes in body weight as well as water and ethanol consumption. These measures were taken at least 5 days per week. We hypothesized that there would be elevated levels of ethanol con-sumption (g ethanol/kg body weight/day) in (a) adolescent vs. adult rats and (b) female vs. male rats. Future research might focus on gene and/or protein expression differences within certain nuclei of the brain’s reward neurocircuit between the FHP and FHN lines of rats. Currently, some data has been collected and statistically analyzed. Upon completion the study re-sults will be prepared for presentation and manuscript submission. Funded in part by the Indiana University-Purdue University Indianapolis, Undergraduate Re-search Opportunities Program (UROP

Caenorhabditis elegans as a model system to identify therapeutics for alcohol use disorders

Alcohol use disorders (AUDs) cause serious problems in society and few effective treatments are available. Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study the neurobiological basis of human behavior with a conserved, fully tractable genome, and a short generation time for fast generation of data at a fraction of the cost of other organisms. C. elegans demonstrate movement toward, and concentration-dependent self-exposure to various psychoactive drugs. The discovery of opioid receptors in C. elegans provided the impetus to test the hypothesis that C. elegans may be used as a medications screen to identify new AUD treatments. We tested the effects of naltrexone, an opioid antagonist and effective treatment for AUDs, on EtOH preference in C. elegans. Six-well agar test plates were prepared with EtOH placed in a target zone on one side and water in the opposite target zone of each well. Worms were treated with naltrexone before EtOH preference testing and then placed in the center of each well. Wild-type worms exhibited a concentration-dependent preference for 50, 70 and 95% EtOH. Naltrexone blocked acute EtOH preference, but had no effect on attraction to food or benzaldehyde in wild-type worms. Npr-17 opioid receptor knockout mutants did not display a preference for EtOH. In contrast, npr-17 opioid receptor rescue mutants exhibited significant EtOH preference behavior, which was attenuated by naltrexone. Chronic EtOH exposure induced treatment resistance and compulsive-like behavior. These data indicate that C. elegans can serve as a model system to identify compounds to treat AUDs

Caenorhabditis elegans Show Preference for Stimulants and Potential as a Model Organism for Medications Screening

The nematode Caenorhabditis elegans (C. elegans) is a popular invertebrate model organism to study neurobiological disease states. This is due in part to the intricate mapping of all neurons and synapses of the entire animal, the wide availability of mutant strains, and the genetic and molecular tools that can be used to manipulate the genome and gene expression. We have shown that, C. elegans develops a conditioned preference for cues that had previously been paired with either cocaine or methamphetamine exposure that is dependent on dopamine neurotransmission, similar to findings using place conditioning with rats and mice. In the current study, we show C. elegans also display a preference for, and self-exposure to, cocaine and nicotine. This substance of abuse (SOA) preference response can be selectively blocked by pretreatment with naltrexone and is consistent with the recent discovery of an opioid receptor system in C. elegans. In addition, pre-exposure to the smoking cessation treatment varenicline also inhibits self-exposure to nicotine. Exposure to concentrations of treatments that inhibit SOA preference/self-exposure did not induce any significant inhibition of locomotor activity or affect food or benzaldehyde chemotaxis. These data provide predictive validity for the development of high-throughput C. elegans behavioral medication screens. These screens could enable fast and accurate generation of data to identify compounds that may be effective in treating human addiction. The successful development and validation of such models would introduce powerful and novel tools in the search for new pharmacological treatments for substance use disorders, and provide a platform to study the mechanisms that underlie addictions

Le FORUM, Vol. 36 No. 4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1035/thumbnail.jp

Le FORUM, Vol. 38 No. 4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1043/thumbnail.jp

Le Forum, Vol. 44 #3

https://digitalcommons.library.umaine.edu/francoamericain_forum/1105/thumbnail.jp

Features, Causes and Consequences of Splanchnic Sequestration of Amino Acid in Old Rats

RATIONALE: In elderly subjects, splanchnic extraction of amino acids (AA) increases during meals in a process known as splanchnic sequestration of amino acids (SSAA). This process potentially contributes to the age-related progressive decline in muscle mass via reduced peripheral availability of dietary AA. SSAA mechanisms are unknown but may involve an increased net utilization of ingested AA in the splanchnic area. OBJECTIVES: Using stable isotope methodology in fed adult and old rats to provide insight into age-related SSAA using three hypotheses: 1) an increase in protein synthesis in the gut and/or the liver, 2) an increase in AA oxidation related to an increased ureagenesis, and 3) Kupffer cell (KC) activation consequently to age-related low-grade inflammation. FINDINGS: Splanchnic extraction of Leu (SPELeu) was doubled in old rats compared to adult rats and was not changed after KC inactivation. No age-related effects on gut and liver protein synthesis were observed, but urea synthesis was lower in old rats and negatively correlated to liver Arg utilization. Net whole-body protein synthesis and arterial AA levels were lower in old rats and correlated negatively with SPELeu. CONCLUSION: SSAA is not the consequence of age-related alterations in ureagenesis, gut or liver protein synthesis or of KC activity. However, SSAA may be related to reduced net whole-body protein synthesis and consequently to the reduced lean body mass that occurs during aging

Corporate reputation in the spanish context: An interaction between reporting to stakeholders and industry.

ABSTRACT: The authors describe the intensity and orientation of the corporate social responsibility (CSR) reporting in four Spanish industries and explore the relationship that exists between both concepts and an independent measurement of reputation for CSR (CSRR). The results demonstrate that the CSR reporting is especially relevant and useful in the finance industry. Finance companies report significantly more CSR information than most industries in Spain, and this reporting is more closely linked to their CSRR than the CSR reporting of basic, consumer goods and services industries. Borra

Paramagnetic and fluorescent liposomes for target-specific imaging and therapy of tumor angiogenesis

Angiogenesis is essential for tumor growth and metastatic potential and for that reason considered an important target for tumor treatment. Noninvasive imaging technologies, capable of visualizing tumor angiogenesis and evaluating the efficacy of angiostatic therapies, are therefore becoming increasingly important. Among the various imaging modalities, magnetic resonance imaging (MRI) is characterized by a superb spatial resolution and anatomical soft-tissue contrast. Revolutionary advances in contrast agent chemistry have delivered versatile angiogenesis-specific molecular MRI contrast agents. In this paper, we review recent advances in the preclinical application of paramagnetic and fluorescent liposomes for noninvasive visualization of the molecular processes involved in tumor angiogenesis. This liposomal contrast agent platform can be prepared with a high payload of contrast generating material, thereby facilitating its detection, and is equipped with one or more types of targeting ligands for binding to specific molecules expressed at the angiogenic site. Multimodal liposomes endowed with contrast material for complementary imaging technologies, e.g., MRI and optical, can be exploited to gain important preclinical insights into the mechanisms of binding and accumulation at angiogenic vascular endothelium and to corroborate the in vivo findings. Interestingly, liposomes can be designed to contain angiostatic therapeutics, allowing for image-supervised drug delivery and subsequent monitoring of therapeutic efficacy