Intermittent access to 20% ethanol induces high ethanol consumption in Long-Evans and Wistar rats

BACKGROUND: There has been some difficulty getting standard laboratory rats to voluntarily consume large amounts of ethanol without the use of initiation procedures. It has previously been shown that standard laboratory rats will voluntarily consume high levels of ethanol if given intermittent-access to 20% ethanol in a 2-bottle-choice setting [Wise, Psychopharmacologia 29 (1973), 203]. In this study, we have further characterized this drinking model. METHODS: Ethanol-naïve Long-Evans rats were given intermittent-access to 20% ethanol (three 24-hour sessions per week). No sucrose fading was needed and water was always available ad libitum. Ethanol consumption, preference, and long-term drinking behaviors were investigated. Furthermore, to pharmacologically validate the intermittent-access 20% ethanol drinking paradigm, the efficacy of acamprosate and naltrexone in decreasing ethanol consumption were compared with those of groups given continuous-access to 10 or 20% ethanol, respectively. Additionally, ethanol consumption was investigated in Wistar and out-bred alcohol preferring (P) rats following intermittent-access to 20% ethanol. RESULTS: The intermittent-access 20% ethanol 2-bottle-choice drinking paradigm led standard laboratory rats to escalate their ethanol intake over the first 5 to 6 drinking sessions, reaching stable baseline consumption of high amounts of ethanol (Long-Evans: 5.1 +/- 0.6; Wistar: 5.8 +/- 0.8 g/kg/24 h, respectively). Furthermore, the cycles of excessive drinking and abstinence led to an increase in ethanol preference and increased efficacy of both acamprosate and naltrexone in Long-Evans rats. P-rats initiate drinking at a higher level than both Long-Evans and Wistar rats using the intermittent-access 20% ethanol paradigm and showed a trend toward a further escalation in ethanol intake over time (mean ethanol intake: 6.3 +/- 0.8 g/kg/24 h). CONCLUSION: Standard laboratory rats will voluntarily consume ethanol using the intermittent-access 20% ethanol drinking paradigm without the use of any initiation procedures. This model promises to be a valuable tool in the alcohol research field.

Partial agonists of the [alpha]3[beta]4[ast] neuronal nicotinic acetylcholine receptor reduce ethanol consumption and seeking in rats

Alcohol use disorders (AUDs) impact millions of individuals and there remain few effective treatment strategies. Despite evidence that neuronal nicotinic acetylcholine receptors (nAChRs) have a role in AUDs, it has not been established which subtypes of the nAChR are involved. Recent human genetic association studies have implicated the gene cluster CHRNA3-CHRNA5-CHRNB4 encoding the α3, α5, and β4 subunits of the nAChR in susceptibility to develop nicotine and alcohol dependence; however, their role in ethanol-mediated behaviors is unknown due to the lack of suitable and selective research tools. To determine the role of the α3, and β4 subunits of the nAChR in ethanol self-administration, we developed and characterized high-affinity partial agonists at α3β4 nAChRs, CP-601932, and PF-4575180. Both CP-601932 and PF-4575180 selectively decrease ethanol but not sucrose consumption and operant self-administration following long-term exposure. We show that the functional potencies of CP-601932 and PF-4575180 at α3β4 nAChRs correlate with their unbound rat brain concentrations, suggesting that the effects on ethanol self-administration are mediated via interaction with α3β4 nAChRs. Also varenicline, an approved smoking cessation aid previously shown to decrease ethanol consumption and seeking in rats and mice, reduces ethanol intake at unbound brain concentrations that allow functional interactions with α3β4 nAChRs. Furthermore, the selective α4β2(*) nAChR antagonist, DHβE, did not reduce ethanol intake. Together, these data provide further support for the human genetic association studies, implicating CHRNA3 and CHRNB4 genes in ethanol-mediated behaviors. CP-601932 has been shown to be safe in humans and may represent a potential novel treatment for AUDs.

Varenicline, an alpha-4 beta-2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking

Abstract Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha4beta2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.

Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats

Abstract RATIONALE: Previous studies have shown that orexin-1/hypocretin-1 receptors play a role in self-administration and cue-induced reinstatement of food, drug, and ethanol seeking. In the current study, we examined the role of orexin-1/hypocretin-1 receptors in operant self-administration of ethanol and sucrose and in yohimbine-induced reinstatement of ethanol and sucrose seeking. MATERIALS AND METHODS: Rats were trained to self-administer either 10% ethanol or 5% sucrose (30 min/day). The orexin-1 receptor antagonist SB334867 (0, 5, 10, 15, 20 mg/kg, i.p.) was administered 30 min before the operant self-administration sessions. After these experiments, the operant self-administration behaviors were extinguished in both the ethanol and sucrose-trained rats. Upon reaching extinction criteria, SB334867 (0, 5, 10 mg/kg, i.p.) was administered 30 min before yohimbine (0 or 2 mg/kg, i.p.). In a separate experiment, the effect of SB334867 (0, 15, or 20 mg/kg, i.p.) on general locomotor activity was determined using the open-field test. RESULTS: The orexin-1 receptor antagonist, SB334867 (10, 15 and 20 mg/kg) decreased operant self-administration of 10% ethanol but not 5% sucrose self-administration. Furthermore, SB334867 (5 and 10 mg/kg) significantly decreased yohimbine-induced reinstatement of both ethanol and sucrose seeking. SB334867 did not significantly affect locomotor activity measured using the open-field test. CONCLUSIONS: The results suggest that inhibition of OX-1/Hcrt-1 receptors modulates operant ethanol self-administration and also plays a significant role in yohimbine-induced reinstatement of both ethanol and sucrose seeking in rats.

Bricolage as a path to innovation for resource constrained new firms

Evidence suggests that both start-up and young firms (henceforth: new firms) – despite typically being resource-constrained – are sometimes able to innovate (Katila & Shane 2005). Such firms are seldom able to invest in expensive innovation processes, which suggests that they may rely on other pathways to innovation. In this paper, we test arguments that “bricolage,” defined as making do by applying combinations of the resources at hand to new problems and opportunities, provides a pathway to innovation for new firms. Our results suggest that variations in bricolage behaviors can provide an explanation of innovation under resource constraints by new firms.

HRM’s impact on innovative work behavior

The importance of innovation to the long-term survival and growth of an organization has been well recognized and acknowledged, and HRM practitioners face a critical challenge to design and implement practices that ensure the behaviors and attitudes necessary for sustained innovation. In this paper, we present the findings from an exploratory study that establish initial indications of links between work design, training and dcvelopment, employee engagement, and innovative work behaviors, setting the agenda for lurther investigation of how spccific HR practices of work design and training and development can supp0l1 employee engagement, and facilitate sustained innovation.

Cyclists' experiences of harassment from motorists : findings from a survey of cyclists in Queensland, Australia

Objective Harassment from motorists is a major constraint on cycling that has been under-researched. We examined incidence and correlates of harassment of cyclists. Methods Cyclists in Queensland, Australia were surveyed in 2009 about their experiences of harassment while cycling, from motor vehicle occupants. Respondents also indicated the forms of harassment they experienced. Logistic regression modeling was used to examine gender and other correlates of harassment. Results Of 1830 respondents, 76% of men and 72% of women reported harassment in the previous 12 months. The most reported forms of harassment were driving too close (66%), shouting abuse (63%), and making obscene gestures/sexual harassment (45%). Older age, overweight/obesity, less cycling experience (< 2 years) and less frequent cycling (< 3 days/week) were associated with less likelihood of harassment, while living in highly advantaged areas (SEIFA deciles 8 or 9), cycling for recreation, and cycling for competition were associated with increased likelihood of harassment. Gender was not associated with reports of harassment. Conclusions Efforts to decrease harassment should include a closer examination of the circumstances that give rise to harassment, as well as fostering road environments and driver attitudes and behaviors that recognize that cyclists are legitimate road users.

Using the Precede-Proceed Model of Health Program Planning in breast cancer nursing research

Aim: In this paper we discuss the use of the Precede-Proceed model when investigating health promotion options for breast cancer survivors. Background: Adherence to recommended health behaviors can optimize well-being after cancer treatment. Guided by the Precede-Proceed approach, we studied the behaviors of breast cancer survivors in our health service area. Data sources: The interview data from the cohort of breast cancer survivors are used in this paper to illustrate the use of Precede-Proceed in this nursing research context. Interview data were collected from June to December 2009. We also searched Medline, CINAHL, PsychInfo and PsychExtra up to 2010 for relevant literature in English to interrogate the data from other theoretical perspectives. Discussion: The Precede-Proceed model is theoretically-complex. The deductive analytic process guided by the model usefully explained some of the health behaviors of cancer survivors, although it could not explicate many other findings. A complementary inductive approach to the analysis and subsequent interpretation by way of Uncertainty in Illness Theory and other psychosocial perspectives provided a comprehensive account of the qualitative data that resulted in contextually-relevant recommendations for nursing practice. Implications for nursing: Nursing researchers using Precede-Proceed should maintain theoretical flexibility when interpreting qualitative data. Perspectives not embedded in the model might need to be considered to ensure that the data are analyzed in a contextually-relevant way. Conclusion: Precede-Proceed provides a robust framework for nursing researchers investigating health promotion in cancer survivors; however additional theoretical lenses to those embedded in the model can enhance data interpretation.

User-representative feature selection for keystroke dynamics

Continuous user authentication with keystroke dynamics uses characters sequences as features. Since users can type characters in any order, it is imperative to find character sequences (n-graphs) that are representative of user typing behavior. The contemporary feature selection approaches do not guarantee selecting frequently-typed features which may cause less accurate statistical user-representation. Furthermore, the selected features do not inherently reflect user typing behavior. We propose four statistical based feature selection techniques that mitigate limitations of existing approaches. The first technique selects the most frequently occurring features. The other three consider different user typing behaviors by selecting: n-graphs that are typed quickly; n-graphs that are typed with consistent time; and n-graphs that have large time variance among users. We use Gunetti’s keystroke dataset and k-means clustering algorithm for our experiments. The results show that among the proposed techniques, the most-frequent feature selection technique can effectively find user representative features. We further substantiate our results by comparing the most-frequent feature selection technique with three existing approaches (popular Italian words, common n-graphs, and least frequent ngraphs). We find that it performs better than the existing approaches after selecting a certain number of most-frequent n-graphs.

The contribution of leadership attributes to large scale, complex project success

Mismanagement of large-scale, complex projects has resulted in spectacular failures, cost overruns, time blowouts, and stakeholder dissatisfaction. We focus discussion on the interaction of key management and leadership attributes which facilitate leaders’ adaptive behaviors. These behaviors should in turn influence adaptive team member behavior, stakeholder engagement and successful project outcomes, outputs and impacts. An understanding of this type of management will benefit from a perspective based in managerial and organizational cognition. The research question we explore is whether successful leaders of large-scale complex projects have an internal process leading to a display of administrative, adaptive, and enabling behaviors that foster adaptive processes and enabling behaviors within their teams and with external stakeholders. At the core of the model we propose interactions of key attributes, namely cognitive flexibility, affect, and emotional intelligence. The result of these cognitive-affective attribute interactions is leadership leading to enhanced likelihood of complex project success.

Weight management and its role in breast cancer rehabilitation

Overweight and obesity are risk factors for post-menopausal breast cancer, and many women diagnosed with breast cancer, irrespective of menopausal status, gain weight after diagnosis. Weight management plays an important role in rehabilitation and recovery since obesity and/or weight gain may lead to poorer breast cancer prognosis, as well as prevalent co-morbid conditions (e.g. cardiovascular disease and diabetes), poorer surgical outcomes (e.g., increased operating and recovery times, higher infection rates, and poorer healing), lymphedema, fatigue, functional decline, and poorer health and overall quality of life. Health care professionals should encourage weight management at all phases of the cancer care continuum as a means to potentially avoid adverse sequelae and late effects, as well as to improve overall health and possibly survival. Comprehensive approaches that involve dietary and behavior modification, and increased aerobic and strength training exercise have shown promise in either preventing weight gain or promoting weight loss, reducing biomarkers associated with inflammation and co-morbidity, and improving lifestyle behaviors, functional status, and quality of life in this high-risk patient population.

Occupational driver safety : conceptualising a leadership-based intervention to improve safe driving performance

Occupational driving crashes are the most common cause of death and injury in the workplace. The physical and psychological outcomes following injury are also very costly to organizations. Thus, safe driving poses a managerial challenge. Some research has attempted to address this issue through modifying discrete and often simple target behaviors (e.g., driver training programs). However, current intervention approaches in the occupational driving field generally do not consider the role of organizational factors in workplace safety. This study adopts the A-B-C framework to identify the contingencies associated with an effective exchange of safety information within the occupational driving context. Utilizing a sample of occupational drivers and their supervisors, this multi-level study examines the contingencies associated with the exchange of safety information within the supervisor-driver relationship. Safety values are identified as an antecedent of the safety information exchange, and the quality of the leader-member exchange relationship and safe driving performance is identified as the behavioral consequences. We also examine the function of role overload as a factor influencing the relationship between safety values and the safety information exchange. Hierarchical Linear Modelling found that role overload moderated the relationship between supervisors’ perceptions of the value given to safety and the safety information exchange. A significant relationship was also found between the safety information exchange and the subsequent quality of the leader-member exchange relationship. Finally, the quality of the leader-member exchange relationship was found to be significantly associated with safe driving performance. Theoretical and practical implications of these results are discussed.

Identifying parent perspectives to guide active travel intervention with small populations : case study in Denver, Colorado

This paper investigates a strategy for guiding school-based active travel intervention. School-based active travel programs address the travel behaviors and perceptions of small target populations (i.e., at individual schools) so they can encourage people to walk or bike. Thus, planners need to know as much as possible about the behaviors and perceptions of their target populations. However, existing strategies for modeling travel behavior and segmenting audiences typically work with larger populations and may not capture the attitudinal diversity of smaller groups. This case study used Q technique to identify salient travel-related attitude types among parents at an elementary school in Denver, Colorado; 161 parents presented their perspectives about school travel by rank-ordering 36 statements from strongly disagree to strongly agree in a normalized distribution, single centered around no opinion. Thirty-nine respondents' cases were selected for case-wise cluster analysis in SPSS according to criteria that made them most likely to walk: proximity to school, grade, and bus service. Analysis revealed five core perspectives that were then correlated with the larger respondent pool: optimistic walkers, fair-weather walkers, drivers of necessity, determined drivers, and fence sitters. Core perspectives are presented—characterized by parents' opinions, personal characteristics, and reported travel behaviors—and recommendations are made for possible intervention approaches. The study concludes that Q technique provides a fine-grained assessment of travel behavior for small populations, which would benefit small-scale behavioral interventions