Acute drug effects on habitual and non-habitual responding in crossed high alcohol preferring mice

RATIONALE: Drug reward plays a central role in acquiring drug-seeking behavior. However, subjects may continue using drugs despite negative consequences because self-administration becomes habitual, and divorced from outcome values. Although a history of drug and alcohol use expedite habit acquisition, and in spite of the fact that self-administration leads to intoxication, the acute effects of drugs on habitual responding are not well understood. OBJECTIVES: We sought to observe how acute ethanol and amphetamine affect the balance between habitual and goal-directed behavior, as measured by a fluid-reinforced operant conditioning task. METHODS: Selectively bred crossed high-alcohol-preferring (cHAP) mice were trained on an operant conditioning task reinforced on a variable interval schedule with 1% banana solution, which was subsequently devalued via LiCl pairing in half the animals. Ethanol (1.0 g/kg), amphetamine (2.0 mg/kg), or saline was administered prior to a post-devaluation test. RESULTS: Overall, mice showed habitual behavior, but when divided into high- or low-responding groups based on training response rates, saline-treated, low-responding animals devalued, while saline-treated high-responding animals did not. Furthermore, amphetamine elicited devaluation even in high-responding animals, while ethanol prevented devaluation even in low-responding animals. CONCLUSIONS: These data show that ethanol shifts animals toward behaving habitually. This may illuminate why alcohol-intoxicated individuals display impaired judgment about the relative merits of drinking, and potentially serve as a mechanism by which intoxicated subjects resume previously devalued behaviors, such as comorbid drug use. These findings also show that high variable interval response rates facilitate a shift from goal-directed to habitual behavior

An Empirical Analysis of the Canadian Term Structure of Zero-Coupon Interest Rates

Zero-coupon interest rates are the fundamental building block of fixed-income mathematics, and as such have an extensive number of applications in both finance and economics. The risk-free government zero-coupon term structure is, however, not directly observable and needs to be generated from the prices of marketable, coupon-bearing bonds. The authors introduce the first public-domain database of constant-maturity zero-coupon yield curves for the Government of Canada bond market. They first outline the mechanics of the curve-fitting algorithm that underlie the model, and then perform some preliminary statistical analysis on the resulting yield curves. The full sample period extends from January 1986 to May 2003; it is broken down into two subsamples, reflecting the structural and macroeconomic changes that impacted the Canadian fixed-income markets over that time. The authors examine the evolution of a number of key interest rates and yield-curve measures over the period, perform a principal-components analysis of the common factors that have influenced yield changes over time, and compare holding-period returns over the sample for assets of various maturities.Financial markets; Interest rates; Econometric and statistical methods

Selected lines and inbred strains. Tools in the hunt for the genes involved in alcoholism

In their quest to elucidate the genetic influences contributing to alcoholism, researchers have long used selected lines and inbred strains of rodents. Selected lines are obtained by repeatedly mating those animals within a population that show extremely high or low values of the desired trait. Inbred strains are generated by mating male and female siblings, irrespective of any particular trait, over several generations. Both of these approaches have provided researchers with extensive knowledge about the genetic and neurobiological mechanisms contributing to alcohol-related traits. However, the use of these models is associated with some limitations, mostly resulting from the inbreeding involved in generating such lines and strains. Nevertheless, these models can offer some advantages over other genetic approaches, such as the analysis of quantitative trait loci or the generation of transgenic and knockout mice

A theoretical study of the aerodynamic characteristics of lifting-body entry vehicles Summary report, Mar. 1965 - Mar. 1966

Aerodynamic characteristics of lifting-body entry vehicle

Periwinkles and parasites: the occurrence and phenotypic effects of parasites in Littorina saxatilis and L. arcana in northeastern England

Littorina saxatilis is a common intertidal gastropod on shores of the North Atlantic, and an 24 important study species for evolutionary investigations. Its congener L. arcana is much less 25 widely distributed, but both species are common at Old Peak, Yorkshire, UK. The parasite 26 profiles of L. saxatilis and L. arcana from this shore were determined histologically, revealing 27 a ciliated protist, Protophrya ovicola, an unidentified apicomplexan (present in <1% L. 28 saxatilis) and three trematode parasites tentatively assigned to Renicola sp., Microphallus 29 similis and M. pygmaeus. The profile data include prevalence information and associated 30 histology. Protophrya ovicola associated predominantly with the wave ecotype of L. saxatilis 31 (65%) rather than the crab ecotype (16%). Microphallus similis occurred at a higher 32 prevalence in the L. arcana population (38%) in comparison with the L. saxatilis population 33 (11%). Overall, there appeared to be a lower prevalence of trematodes in the high-shore L. 34 saxatilis. By modelling occurrence of individual parasites and shell morphometrics, an 35 assessment of parasite-associated morphological change was conducted. We conclude that 36 parasitism appeared not to cause shell-shape change, but rather that snails of a certain shell 37 shape were more likely to display infection. Records of parasites in L. saxatilis and L. arcana 38 are briefly reviewed, showing that the diversity of parasites reported here is relatively low

Pharmacologically relevant intake during chronic, free-choice drinking rhythms in selectively bred high alcohol-preferring mice

Multiple lines of high alcohol-preferring (HAP) mice were selectively bred for their intake of 10% ethanol (v/v) during 24-hour daily access over a 4-week period, with the highest drinking lines exhibiting intakes in excess of 20 g/kg/day. We observed circadian drinking patterns and resulting blood ethanol concentrations (BECs) in the HAP lines. We also compared the drinking rhythms and corresponding BECs of the highest drinking HAP lines to those of the C57BL/6J (B6) inbred strain. Adult male and female crossed HAP (cHAP), HAP replicate lines 1, 2, 3 and B6 mice had free-choice access to 10% ethanol and water for 3 weeks prior to bi-hourly assessments of intake throughout the dark portion of the light-dark cycle. All HAP lines reached and maintained a rate of alcohol intake above the rate at which HAP1 mice metabolize alcohol, and BECs were consistent with this finding. Further, cHAP and HAP1 mice maintained an excessive level of intake throughout the dark portion of the cycle, accumulating mean BEC levels of 261.5 ± 18.09 and 217.9 ± 25.02 mg/dl, respectively. B6 mice drank comparatively modestly, and did not accumulate high BEC levels (53.63 + 8.15 mg/dl). Free-choice drinking demonstrated by the HAP1 and cHAP lines may provide a unique opportunity for modeling the excessive intake that often occurs in alcohol-dependent individuals, and allow for exploration of predisposing factors for excessive consumption, as well as the development of physiological, behavioral and toxicological outcomes following alcohol exposure

Acceptance and commitment therapy delivered in a dyad after a severe traumatic brain injury: a feasibility study

Objective: There is a high prevalence of complex psychological distress after a traumatic brain injury but limited evidence of effective interventions. We examined the feasibility of Acceptance and Commitment Therapy after a severe traumatic brain injury using the criteria, investigating a therapeutic effect, and reviewing the acceptability of measures, treatment protocol, and delivery method (in a dyad of two clients and a therapist). Method: Two male outpatients with severe traumatic brain injury and associated psychological distress jointly engaged in a seven session treatment program based on Acceptance and Commitment Therapy principles. Pre- and post-treatment measures of mood, psychological flexibility, and participation were taken in addition to weekly measures. Results: The intervention showed a therapeutic effect with one participant, and appeared to be acceptable for both participants with regard to program content, measures, and delivery mode by in a dyad. One participant showed both significant clinical and reliable change across several outcome measures including measures of mood and psychological flexibility. The second participant did not show a reduction in psychological inflexibility, but did show a significant drop in negative affect. Significant changes pre- to post-treatment for measures of participation were not indicated. Qualitatively, both participants engaged in committed action set in accordance with their values. Conclusions: This study suggests that Acceptance and Commitment Therapy may be feasible to be delivered in a dyad with individuals who have a severe traumatic brain injury. A further test of its potential efficacy in a phase II clinical trial is recommended

Emotional reactivity to incentive downshift as a correlated response to selection of high and low alcohol preferring mice and an influencing factor on ethanol intake

Losing a job or significant other are examples of incentive loss that result in negative emotional reactions. The occurrence of negative life events is associated with increased drinking (Keyes, Hatzenbuehler, & Hasin, 2011). Further, certain genotypes are more likely to drink alcohol in response to stressful negative life events (Blomeyer et al., 2008; Covault et al., 2007). Shared genetic factors may contribute to alcohol drinking and emotional reactivity, but this relationship is not currently well understood. We used an incentive downshift paradigm to address whether emotional reactivity is elevated in mice predisposed to drink alcohol. We also investigated if ethanol drinking is influenced in High Alcohol Preferring mice that had been exposed to an incentive downshift. Incentive downshift procedures have been widely utilized to model emotional reactivity, and involve shifting a high reward group to a low reward and comparing the shifted group to a consistently rewarded control group. Here, we show that replicate lines of selectively bred High Alcohol Preferring mice exhibited larger successive negative contrast effects than their corresponding replicate Low Alcohol Preferring lines, providing strong evidence for a genetic association between alcohol drinking and susceptibility to the emotional effects of negative contrast. These mice can be used to study the shared neurological and genetic underpinnings of emotional reactivity and alcohol preference. Unexpectedly, an incentive downshift suppressed ethanol drinking immediately following an incentive downshift. This could be due to a specific effect of negative contrast on ethanol consumption or a suppressive effect on consummatory behavior in general. These data suggest that either alcohol intake does not provide the anticipated negative reinforcement, or that a single test was insufficient for animals to learn to drink following incentive downshift. However, the emotional intensity following incentive downshift provides initial evidence that this type of emotional reactivity may be a predisposing factor in alcoholism