Neil E. Rowland - US grants

The concept of "homeostasis" (the idea that the body tends to balance various factors to maintain a stable internal state) is a key part of most current explanations of ingestive behavior, in particular water and salt intake. However, a number of observations, including Dr. Rowland's own, suggest that this is too simple a view of the mechanism and organization of ingestive behaviors. This research project will critically examine the homeostatic model in several new ways, including the use of a sham-drinking rat preparation in which ingested fluids are lost through a tube from the stomach out of the animal. Dr. Rowland and others have shown that water deprivation increases sham drinking more than normal drinking. Surprisingly, however, Dr. Rowland has been unable to produce this greater increase in sham drinking with the presumed elementary thirst stimuli, hypovolemia (low blood volume) and hyperosmolarity (high concentration of chemicals dissolved in the blood). The first experiment will use different routes of administration of salt at different times of day in order to assess the generality of the surprising finding. Dr. Rowland will also examine the microstructure (bursts and pauses) of drinking and attempt to assess the role of very-short-term feedback loops on oral satiety that may override physiologic thirst signals (and thus be independent of the controls of fluid homeostasis). While such oral satiety factors have been suspected for many years, they have never been analyzed convincingly. The second and third experiments will deal with oral versus systemic factors in the control of salt intake, again using sham ingestion as an experimental tool to separate oral from systemic (pre- and post-ingestional) factors. At least two different strains of rats will be studied because of genetic differences in salt preference. Dr. Rowland hopes to be able to assess, from microstructural analysis of sham drinking, the mechanisms by which this genetic difference affects behavior. Dr. Rowland's studies place a new theoretical importance on oral factors as primary mechanisms in maintaining fluid balance and have wider implications for the interplay between systemic states and environmental stimuli in the control of behavior.

9731885 This program will offer summer research experiences in the field of Psychobiology at the University of Florida (UF). Applicants will be solicited by mailings to schools in the Southeast United States, with special emphasis on smaller and/or minority institutions at which students do not otherwise have an opportunity for significant research. Ten participants will be selected and will spend 12 weeks at UF (mid-May through early August). To facilitate group cohesiveness and interaction, they will be housed in an apartment residence on campus. Over the 12 weeks, each participant will complete a research project under the direct supervision of a faculty mentor. The primary faculty will give their time to this program; each has an active research program in psychobiology, with the range of emphasis spanning molecular and animal studies through cognitive neuroscience. In addition to the primary faculty, affiliated faculty, staff, and graduate students will be available to help the participants. Students also will attend a small-group tutorial to cover the essentials of biological psychology, as well as a periodic lecture for the group on topics including ethics, experimental design, and career development. They will learn communicative skills by preparing and presenting oral and written reports.

psychology; nervous system; mother /infant health care; cardiovascular system; Mammalia; biomedical resource; minerals; behavioral /social science research tag;

[unreadable] DESCRIPTION (provided by applicant): Two major classes of addictive disorder in humans relate to nicotine use and to excessive food consumption. The concept of food as a commodity with abuse potential has become popular coincident with the obesity epidemic, but little work has directly compared food with drug reward. The present studies will compare the way in which the internal change resulting from either glucose or nicotine self-administration by rats may be preferentially associated with distinctive oral taste cues. Intravenously (IV) self-administered nicotine is thought to be only a weak reinforcer in rats. In contrast, humans readily become dependent upon nicotine, and withdrawal is difficult. These differences may arise in part because the cues associated with nicotine intake in humans include its flavor while in rat studies the cues are almost always changes in illumination. The main goal of this proposal is to determine whether intravenous self-administration of nicotine by rats is facilitated when a coincident taste or flavor cue is associated with nicotine delivery. First, it is important to establish strictly parallel procedures by which we can compare nicotine with nutrient delivery. The first experiment proposes to modify a published procedure in which intragastric delivery of glucose and water produces a strong sensory preference for a flavor paired with glucose delivery. Rats fitted with intragastric and intraoral catheters will be studied on alternating days in conditions in which consumption of a distinctive flavor cue (the CS+) is associated with delivery of glucose and consumption of a different flavor cue (the CS-) is associated with water infusion. The flavor cue will be delivered either through the rat licking naturally or by a nosepoke response for intraoral delivery of the flavor solution. Preference will be assessed by comparing intakes when both flavors are present. This will be compared with a situation in which illumination changes but no taste cue occur following completion of lever presses. Having identified key parameters, the design will be applied to intravenous delivery of nicotine as the reinforcer. We will again determine whether a nicotine-paired flavor becomes preferred. In the final proposed study, we will determine whether IV glucose as a reinforcer is either similar to or different from either IG glucose or IV nicotine as reinforcer. These studies may help to develop ways in conditioned preferences can be manipulated to prevent or treat certain addictive disorders, including overeating. [unreadable] [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): Overeating and obesity are significant health problems for Americans of all ages. The proposed studies will examine, in mice of normal and obese genetic backgrounds, the effects of imposing economic costs (lever presses) on food intake and patterns of eating. Additionally, we will examine whether prospective appetite suppressant drugs become more effective under conditions of selectively imposed economic costs. Both human and animal models point to multiple causes of obesity, including genetic predispositions to gain weight, ready availability of highly caloric foods, and reduced everyday exercise. Animal models have been instrumental in understanding genetic abnormalities that produce obesity but these models have been tested almost exclusively in environments in which there is no cost associated with obtaining food. In contrast, the evolution of abilities to procure and utilize food in hard times has been critical. It is important to develop and test animal protocols in which the effect of effort on food procurement and consumption are measured, and also to assess the effect of potential treatments in these protocols. Specifically, the protocols that we will use are "closed economy" in which mice must obtain all of their food in that environment. The first aim is to examine in outbred ICR:CD1 mice whether several types of economic cost, simulated by lever pressing as a fixed price (ratio), as a premeal foraging or procurement cost, or as an incrementing cost during the meal (progressive ratio) affect meal patterns. The latter two types of cost are predicted to have opposite effects on meal parameters, so we will also test their combination and develop a brief or streamlined protocol for future testing. The second aim, using the streamlined closed economy protocol, is to test whether mice either heterozygous or homozygous for genetic deletion of melanocortin 4 receptor deletion exhibit altered meal patterns or elasticity of food demand compared with wild type controls. The third aim, again using the streamlined protocol and outbred CD1 mice, is to examine whether chronic treatment with putative anorectic agents affect economic food choices. The agents to be studied are serotonergic agonist dexfenfluramine and the cannabinoid receptor antagonist rimonabant. The proposed studies will be the first to address the issue of behavioral change induced by anorectics under such conditions of simulated economic costs. [unreadable] [unreadable] [unreadable]