1985 — 1987 |
Kiefer, Stephen W |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Taste Cortex Mediation of Alcohol Responses @ Kansas State University
The present research program will continue to examine the involvement of the gustatory neocortex in the mediation of the rat's hedonic and associative response to alcohol solutions. Previous data from our labortory have shown that rats lacking gustatory neocortex consume more alcohol than control rats under schedules of restricted fluid access. Experiments are planned to determine if this hyperresponsiveness in rats lacking gustatory neocortex will be present when animals are given continuous access to aclohol. An additional experiment will determine if body weight and consumption of alcohol for caloric content might account for the hyperresponsiveness. Data collected in the last year also indicate that, although rats lacking gustatory neocortex acquire alcohol aversions normally, they extinguish the aversion faster than controls. Similarly, a preoperatively-instated alcohol aversion was retained following gustatory neocortex ablation but, again, the operated rats extinguished faster than controls. These data indicate that alcohol is not a simple tastant but rather has complex properties. Experiments are proposed to test the hypothesis that the odor of alcohol mediates the learning and retention in rats lacking gustatory neocortex. Because alcohol represents a compound taste and odor stimulus, the scope the present grant is broadened to examine both gustatory and olfactory qualities of alcohol. Each of these component stimuli and their neural basis will be examined in associative tests by separate manipulations: The gustatory aspect of alcohol will be degraded as a cue with gustatory neocortex ablations; the odorant qualities of alcohol will be degraded with olfactory bulbectomy. Because consumption of alcohol represents a serious health problem, study of the neural mechanisms which influence drinking behavior is important and may provide insight to methods for the eventual modification of alcohol consumption.
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1987 — 1995 |
Kiefer, Stephen W |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Taste Reactivity to Alcohol @ Kansas State University
The present research program will examine the taste reactivity of rats to alcohol solutions. Taste reactivity refers specifically to the stereotyped mouth and tongue movements that tastants elicit when infused into the mouth. Individual rats will be implanted with intraoral fistulae through which taste solutions can be infused. As the tastant is applied to the oral cavity, videotape records will be made and scored for the presence to tongue movements, masticatory activity, and overall body movement of the rat. Previous studies have shown that rats exhibit two basic responses to infused tastants: ingestive responses and aversive responses. These responses can be elicited by sucrose solutions and quinine solutions, respectively. The experiments proposed will determine what type of reactivity response alcohol solutions elicit in rats. Preliminary behavioral tests with rats indicate that alcohol has a sweet-bitter taste; rats trained to avoid an alcohol solution generalize the aversion to a sucrose-quinine compound solution. It is hypothesized that the rat's reactivity to alcohol will consist of both ingestive and aversive components which will alternate as the solution stimulates the tongue. Concentration- response functions will be determined to see if the characteristics of the alcohol response is concentration dependent. Further tests will examine whether different pretesting experiences (familiarization, addiction, mild food deprivation, and alcohol- illness conditioning) alter reactivity to alcohol and, if so, precisely how these alterations are demonstrated. The primary rationale for the research program is that little is known about the taste of alcohol. This area of research is important because it is known that the decision whether to ingest or reject a food is ultimately dependent upon the chemical properties of the substance, i.e. the taste. Further, alterations in alcohol consumptions, such as that seen in alcohol addiction, may be accompanied by alterations in taste reactivity, a potentially important result which could affect subsequent treatment programs.
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1999 — 2000 |
Kiefer, Stephen W |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Naltrexone and Alcohol Reactivity @ Kansas State University
Taste represents an important factor in the decision to ingest substances, including alcohol. Attempts to prevent alcohol consumption in the course of therapy for alcoholics would be facilitated if one could render the taste of alcohol as aversive. Naltrexone, an opiate receptor blocker currently used for treatment of alcoholism, appears to have such properties for rats. Rats given naltrexone treatment respond to alcohol is if it were aversive or less palatable, as indicated by taste reactivity tests. Rats given naltrexone treatment respond to alcohol as if it were aversive or less palatable, as indicated by taste reactivity tests. In addition, alcohol consumption is reduced following acute naltrexone treatment when rats are given restricted fluid access. In the present proposal, we will examine further the hypothesis that naltrexone alters the paste perception of alcohol solutions in rats, specifically making it more aversive tasting. Taste reactivity (stereotyped mouth and tongue movements in addition to certain body movements) provides one with a quantitative measure of the hedonic value or palatability of taste solutions. We will examine both random-bred rats and selected lines of rats bred for high-alcohol consumption (high alcohol drinking or HAD rats from Indiana University, alcohol preferring or AA rats from Finland). The effects of low doses of naltrexone on alcohol taste reactivity will be examined in the first experiment. The next two experiments will determine the specificity of naltrexone by testing its effects on taste reactivity to several taste solutions and several alcohol concentrations. The following two experiments involve HAD and AA rats to determine if naltrexone can shift their taste reactivity to a more aversive sequence (and to decrease alcohol consumption under restricted access tests). An additional experiment will ascertain whether naltrexone has the same effect effects on taste reactivity for alcohol-naive versus alcohol- familiar rats. In the last three experiments (involving outbred, HAD, and AA rats, respective), the effects of chronic naltrexone on concurrent alcohol taste reactivity and alcohol consumption will be determined. The ultimate goal of the project is to characterize the taste processes that are affected by naltrexone, a treatment that has show promise for reducing alcohol consumption and preventing future release in humans. It is believed that an agent that can render the taste of alcohol as aversive and reduce its euphoric effects will be more efficacious in discouraging further consumption than either alone. This would represent an important new aspect for the clinical treatment of alcohol use and abuse.
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2002 |
Kiefer, Stephen W |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Lead: Attention, Impulsivity, and Dopamine @ Kansas State University
Although the hypothesis has repeatedly been posed that attention deficits underlie the cognitive impairments produced by Pb, no systematic examination of this assertion has been undertaken in either human cohorts of experimental animals. The current studies directly address in rats the hypothesis that impulsivity/aversion to delay, one of the three clinically- defined sympton domains of attention deficit disorder, may be a particular target of Pb, based on our comparative observations of Pb effects on a fixed ratio (FR) waiting for reward paradigm and a sustained attention task. On the FR wait paradigm, free food deliveries were available at increasing delays following the completion of an FR 50; any response during the waiting component reset the FR requirement. Mean waiting times of Pb-treated rats were 50 percent shorter than controls. While other explanations are feasible, these results could reflect an aversion to delay which was terminated by a response resetting the FR component. These same Pb exposures were without systematic effect in sustained attention task. Impulsivity, as measured in children using self-control procedures, is predicted by increased fixed interval (FI) response rates. Pb exposure reliably increases FI response rates in animal models. Thus, Pb exposure should likewise increase impulsivity in self-control procedures. This proposal seeks to further evaluate the effect of Pb on impulsivity, the role of aversion to delay in mediating it, and the importance of developmental period of exposure in such effects. Studies show that nucleus accumbens (NAC) dopamine (DA) systems modulate FI response rates. Thus, NAC DA should likewise modulate impulsivity if FI response rates are predictive of impulsivity. These studies will also determine the extent to which NAC DA systems modulate impulsivity in a self-control paradigm. Using combined behavioral/microinjection approaches, three hypotheses will be examined: 1) If Pb exposure produces impulsivity, it should increase the choice of small immediate rewards over larger but delayed rewards in self-control paradigm; 2) Delay aversion rather than alternative behavioral mechanisms accounts for the shorter wait times of Pb-exposed rats on the FR wait paradigm; and 3) NAC DA activity will modulate levels of impulsivity. Collectively, these studies will i) enhance the understanding of impulsivity/delay aversion under both normal and Pb-exposed conditions; ii) provide a more precise basis for behavioral and chemical therapeutic strategies; iii) provide models to assess genetic or environmental risk factors in addition to Pb which can be directly extrapolated to pediatric cohorts.
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2017 |
Kiefer, Stephen W |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Alteration and Renovation @ Kansas State University
PROJECT SUMMARY The Alteration and Renovation (A&R) plans will modernize and expand the functionality of the current Behavioral Neuroscience (BN) Core facility, house within the Department of Psychological Sciences at Kansas State University (KSU). This is the only dedicated BN core in Psychology in the State of Kansas. The BN core currently services approximately 30 users including current faculty and their research teams. The A&R will promote expansion of this core to serve approximately 50 users. The A&R of the BN core will directly support two of the primary projects (Cain and Pickens), and will support the pilot grant, post-doctoral training, and scientific exchange network (SEN) programs, and the current community of users that includes the PI/PD. The modernization of the facility will promote the growth of BN into exciting and innovative research areas that incorporate state-of-the-art techniques, including a range of biochemical assays, fluorescent microscopy, stereotaxic surgical techniques such as cannula implants, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), and optogenetics. The overarching goal of the renovations is to promote the ability of C-NAP researchers to compete for extramural funding by incorporating technologies to answer the challenging questions facing modern neuroscience researchers. The primary areas for renovation are the surgery suite, wet laboratories, and cage wash facilities. The surgery suite will be modernized to upgrade our capabilities to perform manipulations of targeted brain regions (e.g., DREADDs, viruses, and optogenetics implants). The wet laboratories and microscopy laboratory will be expanded with the addition of a new perfusion station for brain tissue removal, upgrades to the existing laboratory, and new equipment, such as an alcohol analyzer for measuring blood ethanol level, and two new microscopes for brain tissue assays (a dissection microscope and fluorescent microscope). The cage wash is a critical element for growth of our facility as we do not currently have any in-house cage washing capabilities, but instead rely on sending our cages to the veterinary school?s facility. We will upgrade the current cage wash room and adjacent clean cage storage room with a pass-through cabinet style washer so that we can wash all of our cages in-house. Overall, the renovations will dramatically improve the functionality of our existing BN core and will provide strong support for the growth of research central to the C-NAP mission.
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2017 — 2020 |
Kiefer, Stephen W |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Behavioral Neuroscience Research Core @ Kansas State University
PROJECT SUMMARY The current Behavioral Neuroscience (BN) core facility, housed within the Department of Psychological Sciences at Kansas State University (KSU), is the only dedicated BN core in Psychology in the State of Kansas. The BN core facility will be modernized and augmented through conducting alterations and renovations, and adding major equipment items to expand the capabilities of the facility. The BN core is a fully functional research core that was purpose-built in the early 1980s, and currently services 20-30 users including the BN PhD program. The core facility improvements will focus on the surgery, microscopy, wet laboratory, and cage wash facilities. The upgrades will expand the range of technologies available in the facility, allowing for the inclusion of cutting- edge techniques into current and future research programs. The core is directed by Dr. Stephen Kiefer, a nationally-known researcher in Behavioral Neuroscience in the area of taste-reactivity and alcohol abuse. Dr. Kirkpatrick (the COBRE PI/PD) will serve as associate director of the core to provide additional senior leadership. Additional training and mentoring will be supplied by the COBRE mentoring team, external advisory committee members, and members from the BN collaborative network at KSU. A veterinary technician will provide daily facility cleaning and maintenance, and will meet the animal care and husbandry needs of facility users. The BN core will directly support two of the primary projects (Cain and Pickens), the current community of users (including the PI/PD), potential pilot grant holders, and the additions of new faculty, post-doctoral fellow(s) and graduate students. The expansion of the core facilities will also support Cognitive and Neurobiological Approaches to Plasticity (C-NAP) center programs by providing an excellent training environment for the post-doctoral training program and contributing to the scientific exchange network (SEN) training. Most importantly the BN core upgrades will improve the research infrastructure for animal model research at KSU. Overall, the BN core facility will provide an important component to the attainment of the C-NAP overarching aims by contributing importantly to the success and growth of animal models of plasticity, a central component of C-NAP.
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