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

An Aggregate Stochastic Model Incorporating Individual Dynamics for Predation Movements of Anelosimus Studiosus

In this paper, we discuss methods for developing a stochastic model which incorporates behavior differences in the predation movements of Anelosimus studiosus (a subsocial spider). Stochastic models for animal movement and, in particular, spider predation movement have been developed previously; however, this paper focuses on the development and implementation of the necessary mathematical and statistical methods required to expand such a model in order to capture a variety of distinct behaviors. A least squares optimization algorithm is used for parameter estimation to fit a single stochastic model to an individual spider during predation resulting in unique parameter values for each spider. Similarities and variations between parameter values across the spiders are analyzed and used to estimate probability distributions for the variable parameter values. An aggregate stochastic model is then created which incorporates the individual dynamics. The comparison between the optimal individual models to the aggregate model indicate the methodology and algorithm developed in this paper are appropriate for simulating a range of individualistic behaviors

Selective labeling of serotonin uptake sites in rat brain by (‘Hjcit.alopram contrasted to labeling of multiple sites by [‘H]imipramine.

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Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself

Acute visceral pain relief mediated by A(3)AR agonists in rats: involvement of N-type voltage-gated calcium channels

Pharmacological tools for chronic visceral pain management are still limited and inadequate. A(3) adenosine receptor (A(3)AR) agonists are effective in different models of persistent pain. Recently, their activity has been related to the block of N-type voltage-gated Ca(2+) channels (Ca(v)2.2) in dorsal root ganglia (DRG) neurons. The present work aimed to evaluate the efficacy of A(3)AR agonists in reducing postinflammatory visceral hypersensitivity in both male and female rats. Colitis was induced by the intracolonic instillation of 2,4-dinitrobenzenesulfonic acid (DNBS; 30 mg in 0.25 mL 50% EtOH). Visceral hypersensitivity was assessed by measuring the visceromotor response and the abdominal withdrawal reflex to colorectal distension. The effects of A(3)AR agonists (MRS5980 and Cl-IB-MECA) were evaluated over time after DNBS injection and compared to that of the selective Ca(v)2.2 blocker PD173212, and the clinically used drug linaclotide. A(3)AR agonists significantly reduced DNBS-evoked visceral pain both in the postinflammatory (14 and 21 days after DNBS injection) and persistence (28 and 35 days after DNBS) phases. Efficacy was comparable to effects induced by linaclotide. PD173212 fully reduced abdominal hypersensitivity to control values, highlighting the role of Ca(v)2.2. The effects of MRS5980 and Cl-IB-MECA were completely abolished by the selective A(3)AR antagonist MRS1523. Furthermore, patch-clamp recordings showed that A(3)AR agonists inhibited Ca(v)2.2 in dorsal root ganglia neurons isolated from either control or DNBS-treated rats. The effect on Ca(2+) current was PD173212-sensitive and prevented by MRS1523. A(3)AR agonists are effective in relieving visceral hypersensitivity induced by DNBS, suggesting a potential therapeutic role against abdominal pain

How payment for research participation can be coercive

The idea that payment for research participation can be coercive appears widespread among research ethics committee members, researchers, and regulatory bodies. Yet analysis of the concept of coercion by philosophers and bioethicists has mostly concluded that payment does not coerce, because coercion necessarily involves threats, not offers. In this article we aim to resolve this disagreement by distinguishing between two distinct but overlapping concepts of coercion. Consent- undermining coercion marks out certain actions as impermissible and certain agreements as unenforceable. By contrast, coercion as subjection indicates a way in which someone’s interests can be partially set back in virtue of being subject to another’s foreign will. While offers of payment do not normally constitute consent-undermining coercion, they do sometimes constitute coercion as subjection. We offer an analysis of coercion as subjection and propose three possible practical responses to worries about the coerciveness of payment

Recent breast cancer incidence trends according to hormone therapy use: the California Teachers Study cohort

Abstract Introduction Recent, international declines in breast cancer incidence are unprecedented, and the causes remain controversial. Few data sources can address breast cancer incidence trends according to pertinent characteristics like hormone therapy use history. Methods We used the prospective California Teachers Study to evaluate changes in self-reported use of menopausal hormone therapy (HT) between 1995 to 1996 and 2005 to 2006 and age-adjusted breast cancer incidence among 74,647 participants aged 50 years or older. Breast cancer occurrence was determined by linkage with the California Cancer Registry. Results During 517,286 woman years of follow up, 565 in situ and 2,668 invasive breast cancers were diagnosed. In situ breast cancer incidence rates in this population did not change significantly from 2000 to 2002 to 2003 to 2005, whereas rates of invasive breast cancer declined significantly by 26.0% from 528.0 (95% confidence intervals (CI) = 491.1, 564.9) per 100,000 women in 2000 to 2002 to 390.6 (95% CI = 355.6, 425.7) in 2003 to 2005. The decline in invasive breast cancer incidence rates was restricted to estrogen receptor-positive tumors. In 1996 to 1999 and 2000 to 2002 invasive breast cancer incidence was higher for women who reported current HT use especially estrogen-progestin (EP) use at baseline than for never or past users; but by 2003 to 2005 rates were comparable between these groups. For women who were taking EP in 2001 to 2002,75% of whom had stopped use by 2005 to 2006, incidence had declined 30.6% by 2003 to 2005 (P = 0.001); whereas incidence did not change significantly for those who never took HT (P = 0.33). Conclusions Few data resources can examine prospectively individual HT use and breast cancer diagnosis. Stable in situ breast cancer rates imply consistent levels of screening and suggest recent declines in invasive breast cancer to be explained predominantly by changes in HT use