Enhancing undergraduate education and research in aging to eliminate health disparities (ENGAGED) - A pipeline program to advance diversity in aging research.

The Enhancing Undergraduate Education and Research in Aging to Eliminate Health Disparities (ENGAGED) program takes advantage of the broad, multidisciplinary research established in the area of aging at Wake Forest University School of Medicine and its partner institutions, Wake Forest University and Winston-Salem State University. The ENGAGED program is designed to provide undergraduate students who are underrepresented in the biomedical sciences an opportunity to participate in educational and research training in aging and health disparities. Funded since August 2019, ENGAGED has provided 73 academic year internships and 46 summer internships, with another 8 internships starting in Fall 2023. A total of 61 students (67% female, 64% African American, 21% Hispanic) have participated in the ENGAGED program, reflecting the fact that 49% participate in more than one session or program offering. To date, 38 of the ENGAGED trainees have graduated (100% with a science, technology, engineering, or math degree), 84% of whom are working or pursuing advanced degrees in the biomedical sciences. Given the unique strengths, existing infrastructure, and long-standing collaborations among the partner institutions, the ENGAGED program is helping advance diversity in aging and health disparities research by creating a pipeline for well-trained underrepresented students interested in biomedical research careers.

Regenerative medicine: a vehicle to infuse laboratory-bench modules into an exercise physiology curriculum.

Regenerative medicine is a novel discipline that both excites undergraduates and may be used as a vehicle to expose students to scientific concepts and opportunities. The goal of this article is to describe the implementation of a National Science Foundation-funded Targeted Infusion Project in which underrepresented minority undergraduates are exposed to laboratory-bench skills and summer research opportunities that they may not have encountered otherwise. A 3-wk infusion of laboratory-bench and data presentation skills, in the context of a regenerative medicine/bioengineering project, aimed to engage students and expose them to opportunities as summer researchers and teaching assistants. The infusion aimed to assess the extent to which students improved 1) attitudes toward laboratory-bench-based techniques, using attitudes toward science as a proxy; 2) perceptions of scientific inquiry; 3) intentions to engage in undergraduate research; and 4) intentions to persist in science, technology, engineering, and mathematics (STEM)-related fields. Results indicate that the 3-wk infusion had no effect on science attitudes, but transcribed responses to structured interviews administered after the summer research experience indicated that students who completed summer research projects had positive experiences. Differences in intentions to engage in research were detected between groups of students in different STEM majors, in addition to differences in intentions to pursue a career in science. We describe the implementation of the infusion and briefly discuss quantitative outcomes. We conclude that infusion of laboratory-bench modules in the context of a regenerative medicine/bioengineering project may play a small but important role in increasing (minority) participation and persistence in the STEM pipeline.

Vascular effects of diphenylmethoxypiperidine-derived dopamine uptake inhibitors.

Vascular effects of 4-aryl methoxypiperidinol compounds previously shown to share with cocaine the ability to inhibit the dopamine transporter are described. All the compounds tested inhibit KCl-induced and noradrenaline-dependent contractions in mesenteric arteries ex vivo. Thus, diphenylpyraline and its analogs may have a role as therapeutic options for the treatment of some of the cardiotoxic effects of cocaine intoxications.

Effects of the histamine H1 receptor antagonist and benztropine analog diphenylpyraline on dopamine uptake, locomotion and reward.

Diphenylpyraline hydrochloride (DPP) is an internationally available antihistamine that produces therapeutic antiallergic effects by binding to histamine H1 receptors. The complete neuropharmacological and behavioral profile of DPP, however, remains uncharacterized. Here we describe studies that suggest DPP may fit the profile of a potential agonist replacement medication for cocaine addiction. Aside from producing the desired histamine reducing effects, many antihistamines can also elicit psychomotor activation and reward, both of which are associated with increased dopamine concentrations in the nucleus accumbens (NAc). The primary aim of this study was to investigate the potential ability of DPP to inhibit the dopamine transporter, thereby leading to elevated dopamine concentrations in the NAc in a manner similar to cocaine and other psychostimulants. The psychomotor activating and rewarding effects of DPP were also investigated. For comparative purposes cocaine, a known dopamine transporter inhibitor, psychostimulant and drug of abuse, was used as a positive control. As predicted, both cocaine (15 mg/kg) and an equimolar dose of DPP (14 mg/kg) significantly inhibited dopamine uptake in the NAc in vivo and produced locomotor activation, although the time-course of pharmacological effects of the two drugs was different. In comparison to cocaine, DPP showed a prolonged effect on dopamine uptake and locomotion. Furthermore, cocaine, but not DPP, produced significant conditioned place preference, a measure of drug reward. The finding that DPP functions as a potent dopamine uptake inhibitor without producing significant rewarding effects suggests that DPP merits further study as a potential candidate as an agonist pharmacotherapy for cocaine addiction.

The synthesis and biological evaluation of dopamine transporter inhibiting activity of substituted diphenylmethoxypiperidines.

The synthesis of potent 4-aryl methoxypiperidinol inhibitors of the dopamine transporter is described. Symmetrical para substituents of the benzene rings are important for high potency in binding to the dopamine transporter. 4-[Bis(4-fluorophenyl) methoxy]-1-methylpiperidine has an IC50 of 22.1+/-5.73 nM and increases locomotor activity in mice.

Diphenylpyraline, a histamine H1 receptor antagonist, has psychostimulant properties.

Diphenylpyraline hydrochloride (DPP) is used clinically as an antihistamine drug, but its neurobiological effects are not completely understood. Voltammetry and microdialysis were used to investigate potential actions of DPP on the dopamine system. Voltammetric monitoring of dopamine signals in mouse nucleus accumbens slices showed that DPP (10 microM) markedly inhibited dopamine uptake. There was a 20-fold increase in apparent Km for dopamine uptake, while Vmax was unchanged. Microdialysis experiments demonstrated that DPP (5 mg/kg, i.p.) elevated extracellular dopamine levels (approximately 200%) in mouse nucleus accumbens. DPP (5 and 10 mg/kg) also induced locomotor activation. All of the effects of DPP were comparable with those of cocaine. Taken together, these results indicate that DPP acts as a competitive dopamine transporter inhibitor similar to cocaine.