Ian A. Paul - US grants

DESCRIPTION: (Applicant's Abstract) Substance abuse and liability for HIV-1 infection are closely related. Many abused drugs impair immune function increasing the risk of infection per exposure as well as accelerating the proliferation of the retrovirus. Little is known regarding the effects of retroviral infection on the subjective response to drug administration. It is not clear whether HIV-1 infection increases. decreases or does not affect the user's perception of drug potency and efficacy. This laboratory has made extensive use of the LP-BM5 retroviral analog of AIDS in mice to study the cognitive and behavioral effects of retroviral infection. The murine AIDS (MAIDS) induced by LP-BM5 infection produces rapid and discrete impairment of learning and memory as well as alterations in CNS function. This impairment is produced well before the appearance of MAIDS-induced neurological deficits indicating that deficits result from impairment of acquisition or retrieval rather than motor performance. We have recently demonstrated that these mice can be trained to discriminate phencyclidine from saline in a nose poke. water reward system in a sensitive (Eve = 3mg/kg), robust (> 80% correct response) and specific manner. After in~ction with the LP-BM5 retrovirus, the potency of phencyclidine increases 10-fold with no effect on efficacy or specificity. We propose to determine whether infection of C57BI/6b mice with the LP-BM5 retrovirus alters the potency, efficacy, or specificity of interoceptive discrimination of pharmacological cues relevant to substance abuse. Thus, we will examine the effects of retroviral infection on the ability of mice to detect and respond to common drugs of abuse such as phencyclidines, ethanol, opioids and cocaine. In addition, we will examine the effects of LP-BM5 infection on the response to other drugs of abuse such as benzodiazepines and barbiturates. At monthly intervals, blood samples will be drawn for RT-PCR analysis of LP-BM5 titer. Repeated-measures ANOVA will be used for statistical analysis of pre-and post-infection drug sensitivity. In addition, regression analysis of drug behavioral effects as a function of RT-PCR-derived viral titer will determine the relationship between viral load and drug sensitivity. These studies will: l) provide basic information of the effects of retroviral infections such as LP-BM5 or HIV-l on the sensitivity of organisms to the subjective effects of drugs of abuse; 2) permit us to narrow the focus of future studies of the neurobiological effects of retroviral infection to sites which are behaviorally relevant and: 3) provide a specific focus for future collaborative studies of the effects of HIV- l infection on the subjective response to drugs of abuse in humans.

nitric oxide; psychopharmacology; antidepressants; pharmacokinetics; clinical research;

behavior; biomedical facility; behavioral /social science research tag; clinical research;

dextromethorphan; human therapy evaluation; respiratory reflex; sleep; drug screening /evaluation; respiratory disorder chemotherapy; trachea; bronchus; respiratory infections; larynx; lung; clinical research; human subject;

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The investigators hypothesize that combination and alternating regimens of acetaminophen and ibuprofen will be superior to ibuprofen alone for antipyresis in a single six-hour dosing schedule.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The CPN applies its financial and material resources to the development of our most crucial resource [unreadable]the next generation of neuroscientists. Continued advancement of neuroscience research requires the nurturing, education and training of individuals along the career path to independent research. To accomplish this, the CPN promotes a formal one-on-one mentorship program along with numerous educational opportunities. The CPN Mentoring and Education Core aims to develop early career faculty capable of maintaining the high quality research which characterizes today's neuroscience research community. The CPN is committed to maintaining a strong link between basic research, clinical research, and the clinical setting - the so-called "bench-to-bedside" link. Junior CPN investigators are paired with both a basic science and a clinical mentor. Basic science mentors provide mentees with the theoretical and practical scientific skills that will allow them to compete successfully for independent funding, while clinical mentors ensure that mentee research maintains clinical relevance as it evolves. The Mentoring and Education Core further promotes team approaches to research, through monthly research progress meetings and by facilitating natural collaborations among departments, thus enhancing the multidisciplinary nature of training. With strong mentoring relationships in place, the CPN further supports early career faculty researchers in developing other vital skills including oral and written presentations of research findings, grant writing and post-award grants management. The CPN supports travel to Regional Seminars on Program Funding and Grants Administration sponsored by the National Institutes of Health. Seminars by nationally- and internationally-recognized scholars with expertise in the areas of psychiatric neuroscience emphasized by junior investigator research, as well as scientists with expertise in other areas that are evolving in psychiatric neuroscience, are sponsored as part of the CPN's Distinguished Speakers Seminar Series. Integrity is fundamental to the work of scientists, and the CPN supports the belief that education is the key to promoting scientific integrity. The Mentoring and Education Core addresses the teaching of ethical conduct in a systematic and rigorous manner through a collaborative effort with the Department of Physiology and Biophysics to develop an interdisciplinary course in the responsible conduct of research. Topics in this series cover federal Responsible Conduct of Research policies, current ethical standards, integrity in publishing (authorship, editors'responsibilities, reviewer confidentiality, plagiarism), the humane care and use of animals, mentorship relationships, and collaborative relationships. In this second year of implementation, the course has become part of the UMC School of Graduate Studies in the Health Sciences core curriculum (ID709 [unreadable]Ethics and Professional Skills) and will be attended by trainees in all programs of the School as well as post-doctoral trainees funded by NIH-supported grants. In addition, the M&E Core is developing a complementary seminar series to run monthly throughout the academic year. In these seminars, specific issues will be presented and discussed under the moderation of the directors of the formal course in responsible conduct of research. Together, these mentoring and educational efforts are proving to be an effective program of professional development. As an interactive system, mentoring and education benefits all [unreadable]the mentor, the mentee, the institution and future research initiatives. Mentors pass on their expertise, providing an environment conducive to developing productive, lifelong research careers in psychiatric neuroscience.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cough is the most common reason for an acute care doctor's visit in the United States and may be the most bothersome symptom for children with upper respiratory tract infections (URI). It is particularly troublesome at night because it can adversely affect sleep for both coughing children and their parents. Recent studies and published guidelines have questioned the efficacy of many of the oral over-the-counter treatments for cough and cold symptoms. This has left parents and patients with limited therapeutic options. This study seeks to subjectively evaluate whether Vicks[unreadable] VapoRub[unreadable] (VVR) ointment and a control ointment (petrolatum) are better than no treatment at all for controlling nocturnal cough and cold symptoms in children with URI. It also will determine the effect of the treatments on sleep quality for children with URI and their parents.