Dissertation Deep Dive: Taking the Plunge to Support Graduate Students

This paper will explicate the process and lessons learned of creating a week-long research and writing graduate-student “Dissertation Deep Dive” (DDD) program, and how collaboration across university units was integral to its success. It will also walk the audience through the thought process and steps taken to achieve this week-long research- and writing-intensive program, as well as challenges, opportunities and lessons learned

Eigentümerschaft und der Endowment Effekt bei Kindern und Erwachsenen

Der Endowment-Effekt—d.h. die Verkaufspreise von Eigentümer sind konsistent höher als die Kaufpreise von Nicht-Eigentümern—ist ein robustes Phänomen, das der neoklassischen ökonomischen Theorie widerspricht. Diese Dissertation trägt mit zwei unterschiedlichen Ansätzen zu der Literatur über den Endowment-Effekt bei. Im ersten Teil, erforschen wir die psychologischen Mechanismen hinter dem Konzept der Eigentümerschaft. Das heißt, wir suchen eine Antwort auf die Frage, ob Eigentümerschaft, psychologische Eigentümerschaft, oder sogar beide den Endowment-Effekt verursachen. Auf der Basis von drei Laborexperimenten, in dem wir auf unterschiedliche Art und Weise Eigentümerschaft manipulierten, zeigen wir, dass der Endowment-Effekt unabhängig von psychologischer Eigentümerschaft auftritt. Eigentümerschaft und nicht psychologische Eigentümerschaft scheint also die Ursache des Endowment-Effekts zu sein. Im zweiten Teil dieser Dissertation, tragen wir zu den spärlichen wissenschaftlichen Ergebnissen über den Endowment-Effekt bei Kindern bei. Wir entwickeln dabei eine neue Methode, um den Effekt zu messen—sogenannte Preference-Cards—die auf Standardmaße aus der erwachsenen Forschung basiert, jedoch Kind-gerecht verpackt ist. In zwei Experimente demonstrieren wir, dass Kinder einen Endowment-Effekt zeigen, der signifikant größer ist als der bei Erwachsenen. Zudem zeigen wir, dass die Preference-Card-Methode ein vielversprechendes Maß für das Messen des Endowment-Effekts bei Individuen unterschiedlichen Alters ist, und diskutieren mögliche Vorteile gegenüber dem Standardmaß.The endowment effect—i.e., owners’ selling prices are consistently higher than nonowners’ buying prices—is a robust phenomenon that contradicts neoclassical economic theory. This dissertation contributes to the endowment effect literature with two distinct approaches. With the first, we explore the psychological mechanisms behind the concept of ownership. More specifically, we address the question whether factual ownership, psychological ownership, or both cause the endowment effect. Based on three laboratory experiments, in which we implement different manipulations of ownership, we show that the occurrence of the endowment effect is independent of psychological ownership. We conclude that factual and not psychological ownership causes the endowment effect. With the second approach, we contribute to the sparse findings regarding the presence of the endowment effect in children. We develop a new measure of the endowment effect—preference-cards—that builds on standard measures from the adult literature but involves a scenario that is appropriate for children. In two experiments, we then provide evidence of an endowment effect in children that is significantly larger in magnitude than that observed in adults. We also demonstrate that the preference-cards measure is a sound measure of the endowment effect in individuals of different ages and discuss its advantages over the previously used measure

Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide

Allogeneic stem cell transplantation (SCT) from an HLA-haploidentical relative provides a potentially curative treatment option for hematologic malignancies patients who lack a suitably HLA-matched donor. The greatest challenge to performing HLA-haploidentical SCT has been high rates of graft failure and severe graft-versus-host disease (GVHD). Our group has been exploring high dose, post-transplantation cyclophosphamide (Cy) as prophylaxis of GVHD after nonmyeloablative, HLA-haploidentical bone marrow transplantation, or mini-haploBMT. Among 210 recipients of mini-haploBMT, 87% of patients have experienced sustained donor cell engraftment. The cumulative incidences of grades II-IV acute GVHD and chronic GVHD are 27% and 13%, respectively. Five-year cumulative incidence of non-relapse mortality is 18%, relapse is 55%, and actuarial overall survival and event-free survivals are 35% and 27%, respectively. These outcomes suggest that mini-haploBMT with post-transplantation Cy is associated with acceptably low toxicities and can provide longterm survival, if not cure, for many patients with advanced hematologic malignancies

Involvement of the Lateral Orbitofrontal Cortex in Drug Context-induced Reinstatement of Cocaine-seeking Behavior in Rats

Orbitofrontal cortex (OFC) damage produces impaired decision-making, impulsivity, and perseveration and potentially contributes to compulsive drug seeking in cocaine users. To further explore this phenomenon, we assessed the role of the lateral OFC (lOFC) in drug context-induced cocaine-seeking behavior in the reinstatement model of drug relapse. Rats were trained to lever press for intravenous cocaine infusions in a distinct environmental context (cocaine-paired context) followed by extinction training in a different context (extinction-paired context). Reinstatement of cocaine seeking (non-reinforced lever presses) was assessed in the cocaine context in the absence of response-contingent stimuli. In experiment 1, we evaluated whether acute inhibition of lOFC output alters context-induced cocaine-seeking behavior by infusing the GABAB+A agonists, baclofen+muscimol, or vehicle into the lOFC immediately before exposure to the cocaine-paired context. In experiments 2–3, we assessed how prolonged loss of lOFC output affects drug context-induced cocaine seeking by administering bilateral NMDA or sham lesions of the lOFC either before or after self-administration and extinction training. Remarkably, OFC functional inactivation attenuated, post-training lesions failed to alter, and pre-training lesions potentiated drug context-induced cocaine seeking without altering responding in the extinction context. These results suggest that neural activity in the lOFC promotes context-induced cocaine-seeking behavior. However, prolonged loss of lOFC output enhances the motivational salience of cocaine-paired contextual stimuli likely by eliciting compensatory neuroadaptations, with the effects of post-training lOFC lesions reflecting an intermediate state of compensatory neuroplasticity. Overall, these findings support the idea that OFC dysfunction may promote cue reactivity and enhance relapse propensity in cocaine users

Effects of mGluR1 antagonism in the dorsal hippocampus on drug context-induced reinstatement of cocaine-seeking behavior in rats

The functional integrity of the dorsal hippocampus (DH) is necessary for drug context-induced reinstatement of cocaine seeking. However, the neuropharmacological mechanisms of this phenomenon are poorly understood

Subregion-specific role of glutamate receptors in the nucleus accumbens on drug context-induced reinstatement of cocaine-seeking behavior in rats: Glutamate and cocaine seeking

The functional integrity of the nucleus accumbens (NAC) core and shell is necessary for contextual cocaine-seeking behavior in the reinstatement animal model of drug relapse; however, the neuropharmacological mechanisms underlying this phenomenon are poorly understood. The present study evaluated the contribution of metabotropic glutamate receptor subtype 1 (mGluR1) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor populations to drug context-induced reinstatement of cocaine-seeking behavior. Rats were trained to lever press for un-signaled cocaine infusions in a distinct context followed by extinction training in a different context. Cocaine-seeking behavior (non-reinforced active lever pressing) was then assessed in the previously cocaine-paired and extinction contexts after JNJ16259685 (mGluR1 antagonist: 0.0, 0.6, or 30 pg/0.3 μl/hemisphere) or CNQX (AMPA/kainate receptor antagonist: 0.0, 0.03, or 0.3 μg/0.3 μl/hemisphere) administration into the NAC core, medial or lateral NAC shell, or the ventral caudate-putamen (vCPu, anatomical control). JNJ16259685 or CNQX in the NAC core dose-dependently impaired contextual cocaine-seeking behavior relative to vehicle. Conversely, CNQX, but not JNJ16259685, in the lateral or medial NAC shell attenuated, whereas CNQX or JNJ16259685 in vCPu failed to inhibit, this behavior. The manipulations failed to alter instrumental behavior in the extinction context, general motor activity, or food-reinforced instrumental behavior in control experiments. Thus, glutamate-mediated changes in drug context-induced motivation for cocaine involve distinct neuropharmacological mechanisms within the core and shell subregions of the NAC, with the stimulation of mGlu1 and AMPA/kainate receptors in the NAC core and the stimulation of AMPA/kainate, but not mGlu1, receptors in the NAC shell being necessary for this phenomenon

Dorsal hippocampal regulation of memory reconsolidation processes that facilitate drug context-induced cocaine-seeking behavior in rats

Exposure to a cocaine-paired context increases the propensity for relapse in cocaine users and prompts cocaine-seeking behavior in rats. According to the reconsolidation hypothesis, upon context re-exposure, established cocaine-related associations are retrieved and can become labile. These associations must undergo reconsolidation into long-term memory to effect enduring stimulus control. The dorsal hippocampus (DH), dorsolateral caudate-putamen, and dorsomedial prefrontal cortex are critical for the expression of context-induced cocaine seeking, and these brain regions may also play a role in the reconsolidation of cocaine-related memories that promote this behavior. To test this hypothesis, rats were trained to press a lever for un-signaled cocaine infusions (0.2 mg/infusion, IV) in a distinct environmental context (cocaine-paired context), followed by extinction training in a different context (extinction context). Rats were then re-exposed to the cocaine-paired context for 15 min in order to reactivate cocaine-related memories or received comparable exposure to a novel unpaired context. Immediately thereafter, rats received bilateral microinfusions of the protein synthesis inhibitor anisomycin, the sodium channel blocker tetrodotoxin, or vehicle into one of the above brain regions. After additional extinction training in the extinction context, reinstatement of cocaine-seeking behavior (i.e., non-reinforced lever presses) was assessed in the cocaine-paired context. Tetrodotoxin, but not anisomycin, administered into the DH inhibited drug context-induced cocaine-seeking behavior in a memory reactivation-dependent manner. Other manipulations failed to alter this behavior. These findings suggest that the DH facilitates the reconsolidation of associative memories that maintain context-induced cocaine-seeking behavior, but it is not the site of anisomycin-sensitive memory re-stabilization per se

Contribution of a Mesocorticolimbic Subcircuit to Drug Context-Induced Reinstatement of Cocaine-Seeking Behavior in Rats

Cocaine-seeking behavior triggered by drug-paired environmental context exposure is dependent on orbitofrontal cortex (OFC)–basolateral amygdala (BLA) interactions. Here, we present evidence supporting the hypothesis that dopaminergic input from the ventral tegmental area (VTA) to the OFC critically regulates these interactions. In experiment 1, we employed site-specific pharmacological manipulations to show that dopamine D1-like receptor stimulation in the OFC is required for drug context-induced reinstatement of cocaine-seeking behavior following extinction training in an alternate context. Intra-OFC pretreatment with the dopamine D1-like receptor antagonist, SCH23390, dose-dependently attenuated cocaine-seeking behavior in an anatomically selective manner, without altering motor performance. Furthermore, the effects of SCH23390 could be surmounted by co-administration of a sub-threshold dose of the D1-like receptor agonist, SKF81297. In experiment 2, we examined effects of D1-like receptor antagonism in the OFC on OFC-BLA interactions using a functional disconnection manipulation. Unilateral SCH23390 administration into the OFC plus GABA agonist-induced neural inactivation of the contralateral or ipsilateral BLA disrupted drug context-induced cocaine-seeking behavior relative to vehicle, while independent unilateral manipulations of these brain regions were without effect. Finally, in experiment 3, we used fluorescent retrograde tracers to demonstrate that the VTA, but not the substantia nigra, sends dense intra- and interhemispheric projections to the OFC, which in turn has reciprocal bi-hemispheric connections with the BLA. These findings support that dopaminergic input from the VTA, via dopamine D1-like receptor stimulation in the OFC, is required for OFC–BLA functional interactions. Thus, a VTA–OFC–BLA neural circuit promotes drug context-induced motivated behavior

The Effect of 7,12-dimethylbenz[a]-anthracene (DMBA) on Physical Activity in Female Mice

BACKGROUND: Regular exercise has been shown to reduce the risk of occurrence for certain cancers. In animal models, DMBA is a synthetic carcinogen that has been established as the gold standard for inducing cancerous tumors in rodents. However, it has yet to be established whether DMBA has an effect on voluntary wheel running in mice. If there is an effect, it would confound any experiment which investigates exercise effects on tumor growth. PURPOSE: The overall purpose of this project was to determine if DMBA altered voluntary wheel running in mice. METHODS: All procedures were approved by TAMU IACUC. SENCAR mice breeder pairs (Charles River) and offspring at 3 weeks of age were group housed and randomly assigned to a group receiving the DMBA (n=69) or not receiving the DMBA treatment (n=22). At 4 weeks of age, two running wheels were placed inside the cages and connected to a computer that measured distance and time. The running wheels were mounted to the cage tops of standard rat cages and equipped with a cycling computer (BC8.12, Sigma Sport) to record running distance and duration. The running wheels were plastic and had a 410mm circumference with a solid running surface. From 8 to 14 weeks of age, mice in the DMBA group were gavaged daily with a DMBA dose (20 µg/mouse) dissolved in corn oil. A two way ANOVA was employed to determine the effect of DMBA on activity with factors of time and treatment. RESULTS: DMBA had no effect on the distance (p=0.51) or duration ran (p=0.12), but significantly decreased the speed at which the mice ran (p=0.02). A post-hoc analysis indicated that significant decreases in speed occurred at weeks 12 (35.2 ±9.2 vs. 46.4 ± 14.6; p=0.0002) and 20 (35.4 ±10.3 vs. 46.2 ± 14.1; p\u3c0.0001) of age. CONCLUSION: Our data suggest that DMBA does not affect the distance or time spent running on a wheel, but does affect the speed at which the mice run. While DMBA decreased speed, the significant effects on speed are minor given that neither distance nor duration were different between the groups. Therefore, we can conclude that DMBA does not prevent voluntary wheel running in mice