Mechanisms of Individual Differences in Impulsive and Risky Choice in Rats

Citation: Kirkpatrick, K., Marshall, A. T., & Smith, A. P. (2015). Mechanisms of Individual Differences in Impulsive and Risky Choice in Rats. Comparative Cognition & Behavior Reviews, 10. Retrieved from http://comparative-cognition-and-behavior-reviews.org/2015/vol10_kirkpatrick_marshall_smith/Mechanisms of Individual Differences in Impulsive and Risky Choice in Rats Kimberly Kirkpatrick Department of Psychological Sciences, Kansas State University Andrew T. Marshall Department of Psychological Sciences, Kansas State University Aaron P

Allostatic load and pain severity in older adults:Results from the English Longitudinal Study of Ageing

Pain is common in older adults, is frequently experienced as stressful, and is associated with increased morbidity and mortality. Stress regulatory systems are adaptive to challenge and change, allostasis, until demands exceed the adaptive capacity contributing to dysregulation, resulting in a high allostatic load. A high allostatic load is associated with increased risk of morbidity and mortality. Pain severity, based on the average intensity of frequent pain, was hypothesized to be positively associated with AL. Four formulations of AL were investigated. Cross-sectional data from Wave 4 (2008-2009) of the English Longitudinal Study of Aging (ELSA) were analyzed. Covariates in the model included age, sex, education, smoking status, alcohol consumption, activity level, depression and common comorbid health conditions. A total of 5341 individuals were included; mean age 65.3(±9.2) years, 55% female, 62.4% infrequent or no pain, 12.6% mild pain, 19.1% moderate pain, and 5.9% severe pain. Severe pain was associated with greater AL defined by all four formulations. The amount of variance explained by pain severity and the covariates was highest when allostatic load was defined by the high risk quartile (12.9%) and by the clinical value (11.7%). Findings indicate a positive relationship between pain severity and AL. Further investigation is needed to determine if there is a specific AL signature for pain that differs from other health conditions

Individual differences in impulsive and risky choice: effects of environmental rearing conditions

The present experiment investigated early-rearing environment modulation of individual differences in impulsive and risky choice. Rats were reared in an isolated condition (IC; n = 12), in which they lived alone without novel stimuli, or an enriched condition (EC; n = 12), in which they lived among conspecifics with novel stimuli. The impulsive choice task involved choices between smaller-sooner (SS) versus larger-later (LL) rewards. The risky choice task involved choices between certain-smaller (C-S) versus uncertain-larger (U-L) rewards. Following choice testing, incentive motivation to work for food was measured using a progressive ratio task and correlated with choice behavior. HPLC analyses were conducted to determine how monoamine concentrations within the prefrontal cortex (PFC) and nucleus accumbens (NAC) related to behavior in different tasks. IC rats were more impulsive than EC rats, but they did not differ in risky choice behavior. However, choice behavior across tasks was significantly correlated (i.e., the more impulsive rats were also riskier). There were no group differences in monoamine levels, but noradrenergic and serotonergic concentrations were significantly correlated with impulsive and risky choice. Furthermore, serotonin and norepinephrine concentrations in the NAC significantly correlated with incentive motivation and the timing of the reward delays within the choice tasks. These results suggest a role for domain general processes in impulsive and risky choice and indicate the importance of the NAC and/or PFC in timing, reward processing, and choice behavior

Evaluation of Content and Accessibility of Orthopaedic Trauma Fellowship Websites

Background: Residents frequently use the internet to find material on fellowship programs. The Orthopaedic Trauma Association (OTA) website serves as a central hub for information on an orthopaedic trauma fellowship (OTF). This study aims to evaluate the accessibility, content, and perceived importance of OTF websites. Methods: We reviewed the 49 OTFs accredited by the OTA fellowship database as of January 2014. We searched for corresponding OTF websites by using the provided OTA hyperlinks and conducting a separate Google search of program location and institution. Links to websites of general orthopaedic programs were not counted. Content of OTF websites was analyzed by noting the presence or absence of specific items in fellow education (11 items) and recruitment (5 items). Results: Of 49 OTFs, a total of 39 (80%) websites specific to the fellowship were identified by searching the OTA database and Google browser. Seven (14%) programs listed on the OTA database provided links directly to fellowship programs. Most programs (28; 57%) did not provide links to specific OTFs or provided non-functional links on the OTA website. Of the 39 accessible OTF websites, a total of 24 (61%) had complete information regarding recruitment and 14 (36%) provided complete details on education. Conclusions: Most accredited OTFs do not adequately use the internet to provide easily accessible and complete information. Further details (especially regarding the role, education, and schedule) would help prospective candidates in thoroughly evaluating programs. The discrepancy in content and accessibility can hinder prospective fellows from appropriately investigating fellowship programs

Mice Lacking Gpr37 Exhibit Decreased Expression of the Myelin-Associated Glycoprotein Mag and Increased Susceptibility to Demyelination

GPR37 is an orphan G protein-coupled receptor that is predominantly expressed in the brain and found at particularly high levels in oligodendrocytes. GPR37 has been shown to exert effects on oligodendrocyte differentiation and myelination during development, but the molecular basis of these actions is incompletely understood and moreover nothing is known about the potential role(s) of this receptor under demyelinating conditions. To shed light on the fundamental biology of GPR37, we performed proteomic studies comparing protein expression levels in the brains of mice lacking GPR37 and its close relative GPR37-like 1 (GPR37L1). These studies revealed that one of the proteins most sharply decreased in the brains of Gpr37/Gpr37L1 double knockout mice is the myelin-associated glycoprotein MAG. Follow-up Western blot studies confirmed this finding and demonstrated that genetic deletion of Gpr37, but not Gpr37L1, results in strikingly decreased brain expression of MAG. Further in vitro studies demonstrated that GPR37 and MAG form a complex when expressed together in cells. As loss of MAG has previously been shown to result in increased susceptibility to brain insults, we additionally assessed Gpr37-knockout (Gpr37−/−) vs. wild-type mice in the cuprizone model of demyelination. These studies revealed that Gpr37−/− mice exhibit dramatically increased loss of myelin in response to cuprizone, yet do not show any increased loss of oligodendrocyte precursor cells or mature oligodendrocytes. These findings reveal that loss of GPR37 alters oligodendrocyte physiology and increases susceptibility to demyelination, indicating that GPR37 could be a potential drug target for the treatment of demyelinating diseases such as multiple sclerosis

The X-ray Reflectors in the Nucleus of the Seyfert Galaxy NGC 1068

(abridged) Based on observations of the Seyfert nucleus in NGC1068 with ASCA, RXTE and BeppoSAX, we report the discovery of a flare (increase in flux by a factor of ~1.6) in the 6.7 keV Fe K line component between observations obtained 4 months apart, with no significant change in the other (6.21, 6.4, and 6.97 keV) Fe K_alpha line components. During this time, the continuum flux decreased by ~20%. The RXTE spectrum requires an Fe K absorption edge near 8.6 keV (Fe XXIII - XXV). The spectral data indicate that the 2-10 keV continuum emission is dominated (~2/3 of the luminosity) by reflection from a previously unidentified region of warm, ionized gas located <~ 0.2 pc from the AGN. The remaining ~1/3 of the observed X-ray emission is reflected from optically thick, neutral gas. The inferred properties of the warm reflector (WR) are: size (diameter) ~ 10^{5.5} /cm3, ionization parameter xi approx 10^{3.5} erg cm/s, and covering fraction 0.003 (L_0/10^{43.5} erg/s)^{-1} < (Omega/4 pi) < 0.024 (L_0/10^{43.5})^{-1}, where L_0 is the intrinsic 2-10 keV X-ray luminosity of the AGN. We suggest that the WR gas is the source of the (variable) 6.7 keV Fe line emission, and the 6.97 keV Fe line emission. The 6.7 keV line flare is assumed to be due to an increase in the emissivity of the WR gas from a decrease (by 20-30%) in L_0. The properties of the WR are most consistent with an intrinsically X-ray weak AGN with L_0 approx 10^{43.0} erg/s. The optical and UV emission that scatters from the WR into our line of sight is required to suffer strong extinction, which can be reconciled if the line-of-sight skims the outer surface of the torus. Thermal bremsstrahlung radio emission from the WR may be detectable in VLBA radio maps of the NGC 1068 nucleus.Comment: 39 pages (9 postscript figures) AASTEX, ApJ, accepte

ICA model order selection of task co-activation networks

Independent component analysis (ICA) has become a widely used method for extracting functional networks in the brain during rest and task. Historically, preferred ICA dimensionality has widely varied within the neuroimaging community, but typically varies between 20 and 100 components. This can be problematic when comparing results across multiple studies because of the impact ICA dimensionality has on the topology of its resultant components. Recent studies have demonstrated that ICA can be applied to peak activation coordinates archived in a large neuroimaging database (i.e., BrainMap Database) to yield whole-brain task-based co-activation networks. A strength of applying ICA to BrainMap data is that the vast amount of metadata in BrainMap can be used to quantitatively assess tasks and cognitive processes contributing to each component. In this study, we investigated the effect of model order on the distribution of functional properties across networks as a method for identifying the most informative decompositions of BrainMap-based ICA components. Our findings suggest dimensionality of 20 for low model order ICA to examine large-scale brain networks, and dimensionality of 70 to provide insight into how large-scale networks fractionate into sub-networks. We also provide a functional and organizational assessment of visual, motor, emotion, and interoceptive task co-activation networks as they fractionate from low to high model-orders

Potential Drug Abuse Therapeutics Derived from the Hallucinogenic Natural Product Salvinorin A

Previous structure-activity relationship studies of salvinorin A have shown that modification of the acetate functionality off the C-2 position to a methoxy methyl or methoxy ethyl ether moiety leads to increased potency at KOP receptors. However, the reason for this increase remains unclear. Here we report our efforts towards the synthesis and evaluation of C-2 constrained analogs of salvinorin A. These analogs were evaluated at opioid receptors in radioligand binding experiments as well as in the GTP-γ-S functional assay. One compound, 5, was found to have affinity and potency at κ opioid (KOP) receptors comparable to salvinorin A. In further studies, 5 was found to attenuate cocaine-induced drug seeking behavior in rats comparably to salvinorin A. This finding represents the first example of a salvinorin A analog that has demonstrated anti-addictive capabilities