Failure of Intravenous Morphine to Serve as an Effective Instrumental Reinforcer in Dopamine D2 Receptor Knock-Out Mice

The rewarding effects of opiates are thought to be mediated through dopaminergic mechanisms in the ventral tegmental area, dopamine-independent mechanisms in the nucleus accumbens, or both. The purpose of the present study was to explore the contribution of dopamine to opiate-reinforced behavior using D2 receptor knock-out mice. Wild-type, heterozygous, and D2 knock-out mice were first trained to lever press for water reinforcement and then implanted with intravenous catheters. The ability of intravenously delivered morphine to maintain lever pressing in these mice was studied under two schedules of reinforcement: a fixed ratio 4 (FR4) schedule (saline, 0.1, 0.3, or 1.0 mg/kg, per injection) and a progressive ratio (PR) schedule (1.0 mg/kg, per injection). In the wild-type and heterozygous mice, FR4 behavior maintained by morphine injections was significantly greater than behavior maintained by vehicle injections. Response rate was inversely related to injection dose and increased significantly in the wild-type and heterozygous mice when the animals were placed on the PR schedule. In contrast, the knock-out mice did not respond more for morphine than for saline and did not respond more when increased ratios were required by the PR schedule. Thus, morphine served as a positive reinforcer in the wild-type and heterozygous mice but failed to do so in the knock-out mice. Under this range of doses and response requirements, the rewarding effects of morphine appear to depend critically on an intact D2 receptor systemFil: Elmer, Greg I.. University of Maryland; Estados UnidosFil: Pieper, Jeanne O.. National Institutes of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Low, Malcolm J.. Oregon Health and Sciences University; Estados UnidosFil: Grandy, David K.. Oregon Health and Sciences University; Estados UnidosFil: Wise, Roy A.. National Institutes of Health; Estados Unido

Dysfunctional Light-Evoked Regulation of cAMP in Photoreceptors and Abnormal Retinal Adaptation in Mice Lacking Dopamine D4 Receptors

Dopamine is a retinal neuromodulator that has been implicated in many aspects of retinal physiology. Photoreceptor cells express dopamine D4 receptors that regulate cAMP metabolism. To assess the effects of dopamine on photoreceptor physiology, we examined the morphology, electrophysiology, and regulation of cAMP metabolism in mice with targeted disruption of the dopamine D4 receptor gene. Photoreceptor morphology and outer segment disc shedding after light onset were normal in D4 knock-out (D4KO) mice. Quinpirole, a dopamine D2/ D3/D4 receptor agonist, decreased cAMP synthesis in retinas of wild-type (WT) mice but not in retinas of D4KO mice. In WT retinas, the photoreceptors of which were functionally isolated by incubation in the presence of exogenous glutamate, light also suppressed cAMP synthesis. Despite the similar inhibition of cAMP synthesis, the effect of light is directly on the photoreceptors and independent of dopamine modulation, because it was unaffected by application of the D4 receptor antagonist L-745,870. Nevertheless, compared with WT retinas, basal cAMP formation was reduced in the photoreceptors of D4KO retinas, and light had no additional inhibitory effect. The results suggest that dopamine, via D4 receptors, normally modulates the cascade that couples light responses to adenylyl cyclase activity in photoreceptor cells, and the absence of this modulation results in dysfunction of the cascade. Dark-adapted electroretinogram (ERG) responses were normal in D4KO mice. However, ERG b-wave responses were greatly suppressed during both light adaptation and early stages of dark adaptation. Thus, the absence of D4 receptors affects adaptation, altering transmission of light responses from photoreceptors to inner retinal neurons. These findings indicate that dopamine D4 receptors normally play a major role in regulating photoreceptor cAMP metabolism and adaptive retinal responses to changing environmental illumination.Fil: Nir, Izhak. The University of Texas Health Science Center; Estados UnidosFil: Harrison, Joseph M.. The University of Texas Health Science Center; Estados UnidosFil: Haque, Rashidul. Emory University School of Medicine; Estados UnidosFil: Low, Malcolm J.. Oregon Health and Science University; Estados UnidosFil: Grandy, David K.. Oregon Health and Science University; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Iuvone, P. Michael. Emory University School of Medicine; Estados Unido

Teaching inductively: games in the tertiary classroom

Inductive teaching methods, where students construct models rather than being told facts, are aids to deeper learning, but are notoriously difficult to incorporate into mainstream tertiary teaching. Games present a relatively painless path to engage and motivate students to actively participate in the learning process. This paper presents a brief reflection on the background of, and motivation for, using games as tools for inductive teaching. The intent here is to provide examples of how games can be incorporated into a curriculum, along with some commentary on the challenges which may be encountered during development and implementation, based on the experiences of the author

Student perceptions of lecture approaches in first-year Engineering Physics

A cohort of first-year Engineering Physics students was surveyed to explore student attitudes towards a variety of large-class lecture techniques, in the first four weeks of their tertiary education. The results are compared with previous studies of the preferred learning style of undergraduate engineering classes. Particular attention is given to student attitudes towards the use of a Personal Response System, as compared to more traditional lecture approaches

Emotional orienting during interoceptive threat in orthostatic intolerance: dysautonomic contributions to psychological symptomatology in the postural tachycardia syndrome and vasovagal syncope

Cognitive and emotional processes are influenced by interoception (homeostatic somatic feedback), particularly when physiological arousal is unexpected and discrepancies between predicted and experienced interoceptive signals may engender anxiety. Due to the vulnerability for comorbid psychological symptoms in forms of orthostatic intolerance (OI), this study investigated psychophysiological contributions to emotional symptomatology in 20 healthy control participants (13 females, mean age 36 ± 8 years), 20 postural tachycardia syndrome (PoTS) patients (18 females, mean age 38 ± 13 years) and 20 vasovagal syncope (VVS) patients (15 females, mean age 39 ± 12 years). We investigated indices of emotional orienting responses (OR) to randomly presented neutral, pleasant and unpleasant images in the supine position and during the induced interoceptive threat of symptom provocation of head-up tilt (HUT). PoTS and VVS patients produced greater indices of emotional responsivity to unpleasant images and, to a lesser degree, pleasant images, during interoceptive threat. Our findings are consistent with biased deployment of response-focused emotion regulation (ER) while patients are symptomatic, providing a mechanistic underpinning of how pathological autonomic overexcitation predisposes to anxiogenic traits in PoTS and VVS patients. This hypothesis may improve our understanding of why orthostasis exacerbates cognitive symptoms despite apparently normal cerebral autoregulation, and offer novel therapeutic targets for behavioural interventions aimed at reducing comorbid cognitive-affective symptoms in PoTS and VVS

A low-pain assessment model for laboratories and tutorials

Continuous assessment motivates students to become engaged with coursework, but presents challenges for staff due to the workload involved in marking and delivering feedback. Care must be taken to avoid students concentrating on simply accumulating marks, to the detriment of learning. We present a Checkpoint assessment model which strives to find a balance between these factors, and show how the Checkpoint model can be applied in tutorial and laboratory environments. Based on an evaluation of changes to student attitudes and performance within a large first-year physics course, we conclude that the Checkpoint model is effective at improving both student satisfaction and results

Post‐traumatic stress disorder and birthweight: methodological challenges

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89463/1/j.1471-0528.2011.03200.x.pd

Persistent gender gaps in first-year physics assessment questions

In a review of six years of first-year physics assessment results, we have identified a number of individual questions which display a persistent gender gap in performance: the facility displayed by males on these questions is consistently higher than that displayed by females. We have looked for patterns in student answers to these questions by gender and overall performance, and identified reasons why these questions might be more challenging for females. Our results indicate that the presentation and wording of questions can result in undesirable cueing, particularly when words and concepts such as ‘positive’ need to be uncoupled from their near-synonyms (such as ‘upwards’ and ‘increasing’) to be correctly applied in a physics context. The observations presented here suggest that this issue is more significant for females than it is for males. Since individual questions may contribute disproportionately to any overall gender gap in assessment, we encourage other educators to review their own historical records and assessment questions

Smart girls know how to use a screwdriver

The gender gap in the physical sciences is well known, with consistent gaps in performance on many assessment types, including standard tests. Many possible reasons for the gap have been proposed, including innate differences in males and females, and differences in experiences. In this paper we examine in detail the gender gap on one particular multiple choice question from the 2013 Australian Science Olympiads Examination for Physics, which asks how a tight screw can most effectively be loosened. The question is easily answered if one has experience of using a screwdriver; otherwise, an exceptional understanding of torque and friction is required to correctly answer the question. We find that there are different choices of distractors by males and females and that while males perform better on this question than females overall, the gender gap reverses for high achieving students. This may indicate that very high-achieving girls are more likely than very high-achieving boys to have experience using a screwdriver. We conclude that providing experience using hand tools would be of benefit to all students, male and female