Neurobehavioral Control of Body Fluid Balance in Mouse

Summary

Principal Investigator: A K Johnson
Abstract: Body fluid homeostasis depends on reflexes that modulate the rate of renal water and sodium loss and on ingestive behaviors (i.e., thirst and salt appetite) that correct homeostatic deficits. Although renal mechanisms slow fluid loss, the restoration of vascular volume depends on the ingestion of water and solute (e.g., sodium). The maintenance of extracellular volume requires that the central nervous system (CNS) receives and processes information about the status of body water and sodium. Several visceral sensory systems provide this afferent input, but there is only a very limited understanding about how this information is handled by the CNS. The present proposal builds upon our prior studies that have been directed at defining the nature of interactions of afferent signals involved in body fluid and cardiovascular homeostasis and at understanding the CNS processing mechanisms of such afferent information. Recently, we have used the mouse to investigate several issues related to body fluid and cardiovascular homeostasis. Use of this species was prompted by the potential of new experimental models derived by manipulation of the mouse genome. Several of our initial studies have adapted and validated many of the conventional experimental manipulations used to study thirst and salt appetite in rat. The results indicate that there are many important similarities between mouse and other experimental species, and also provocative differences. We propose studies in normal mice that allow us to clarify understanding of the control of thirst and salt appetite in this species. In addition we propose studies that take advantage of currently available mouse models to generate important new information about the basic neurobiology of thirst and salt appetite. Specifically, we will study the interaction of the systemic and brain renin-angiotensin-aldosterone systems and blood pressure in the control of their behaviors that contribute to body fluid homeostasis. Initial studies will employ methods and knowledge derived from studying wild type mice to further understanding of the role of body and brain renin-angiotensin systems in the behavioral control of body fluid balance. Other studies will make use of a mouse transgenic model developed at the University of Iowa that over-expresses angiotensin type 1 receptors in brain and in sensory circumventricular organ neurons. Information generated from these studies will be relevant to the well-being of normal individuals exposed to physiological (e.g., exercise) and environmental (e.g., heat) challenges. These studies will be especially important for understanding mechanisms underlying pathological conditions such as hypertension and congestive heart failure where excess thirst and sodium intake have been documented.
Funding Period: 2005-03-01 - 2010-01-31
more information: NIH RePORT

Top Publications

  1. pmc Effects of aging on mineralocorticoid-induced salt appetite in rats
    Robert L Thunhorst
    Departments of Psychology
    Am J Physiol Regul Integr Comp Physiol 305:R1498-505. 2013
  2. ncbi Voluntary running-wheel exercise decreases the threshold for rewarding intracranial self-stimulation
    Michael J Morris
    Department of Psychology, The University of Iowa, Iowa City 52242 1407, USA
    Behav Neurosci 126:582-7. 2012
  3. pmc Non-NMDA receptors in the lateral parabrachial nucleus modulate sodium appetite
    Juliana I F De Gobbi
    Department of Psychology, Cardiovascular Center, University of Iowa, Iowa City, 52242 1407, USA
    Brain Res 1301:44-51. 2009
  4. pmc Mineralocorticoid receptor antagonism prevents hedonic deficits induced by a chronic sodium appetite
    Michael J Morris
    Department of Psychology, Integrative Physiology and Pharmacology, and the Cardiovascular Center, The University of Iowa, Iowa City, IA 52242 1407, USA
    Behav Neurosci 124:211-24. 2010
  5. pmc Drinking and arterial blood pressure responses to ANG II in young and old rats
    Robert L Thunhorst
    Dept of Psychology, Univ of Iowa, 11 Seashore Hall E, Iowa City, IA 52242 1407, USA
    Am J Physiol Regul Integr Comp Physiol 299:R1135-41. 2010
  6. pmc The brain Renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance
    Justin L Grobe
    Department of Internal Medicine, University of Iowa, Iowa City, 52242, USA
    Cell Metab 12:431-42. 2010
  7. pmc Central interactions of aldosterone and angiotensin II in aldosterone- and angiotensin II-induced hypertension
    Baojian Xue
    Department of Psychology, Cardiovascular Center, University of Iowa, 11 Seashore Hall E, Iowa City, IA 52242, USA
    Am J Physiol Heart Circ Physiol 300:H555-64. 2011
  8. pmc Cancer induces inflammation and depressive-like behavior in the mouse: modulation by social housing
    Donald M Lamkin
    Department of Psychology, University of Iowa, IA, USA
    Brain Behav Immun 25:555-64. 2011
  9. pmc Effects of β-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats
    Robert L Thunhorst
    Dept of Psychology, Univ of Iowa, 11 Seashore Hall E, Iowa City, IA 52242 1407, USA
    Am J Physiol Regul Integr Comp Physiol 300:R1001-8. 2011
  10. pmc Behavioral cross-sensitization between DOCA-induced sodium appetite and cocaine-induced locomotor behavior
    Martin J Acerbo
    Departments of Psychology, Pharmacology, and Health and Human Physiology, and the Cardiovascular Center, The University of Iowa, Iowa City, IA 52242, USA
    Pharmacol Biochem Behav 98:440-8. 2011

Scientific Experts

  • ROBERT THUNHORST
  • Baojian Xue
  • A K Johnson
  • Elisa S Na
  • Angela J Grippo
  • Patrick J Lacolley
  • Daniel Badauê-Passos
  • Terry G Beltz
  • Michael J Morris
  • Erin J Whalen
  • Douglas G Whyte
  • Ralph F Johnson
  • Stephen J Lewis
  • M Singh
  • Donald M Lamkin
  • Martin J Acerbo
  • Justin L Grobe
  • Juliana I F De Gobbi
  • Minati Singh
  • Jose Vanderlei Menani
  • Julia A Moffitt
  • Juliana Irani Fratucci De Gobbi
  • J I F De Gobbi
  • Olga S Possas
  • Emilio de Castro e Silva
  • Claudia M Santos
  • Susan K Lutgendorf
  • K Agassandian
  • M B Zimmerman
  • Anil K Sood
  • M M Singh
  • David Lubaroff
  • Daniel R Thedens
  • Curt D Sigmund
  • Scott G Westphal
  • Donald A Morgan
  • Lisa A Cassis
  • CONNIE L GROBE
  • Koji Sakai
  • Huiping Li
  • Kamal Rahmouni
  • Di Xu
  • Allyn L Mark
  • Willem J de Lange
  • M Bridget Zimmerman
  • J Vanderlei Menani
  • T G Beltz
  • L A De Luca
  • G Martinez
  • S P Barbosa
  • James N Bates
  • Josmara B Fregoneze
  • Timothy J Brennan

Detail Information

Publications39

  1. pmc Effects of aging on mineralocorticoid-induced salt appetite in rats
    Robert L Thunhorst
    Departments of Psychology
    Am J Physiol Regul Integr Comp Physiol 305:R1498-505. 2013
    ..There was evidence of impaired renal function in old rats, but this did not account for the reduced saline intakes of the oldest rats. ..
  2. ncbi Voluntary running-wheel exercise decreases the threshold for rewarding intracranial self-stimulation
    Michael J Morris
    Department of Psychology, The University of Iowa, Iowa City 52242 1407, USA
    Behav Neurosci 126:582-7. 2012
    ..We conclude that long-term voluntary exercise increases sensitivity to rewarding stimuli, which may contribute to its antidepressant properties...
  3. pmc Non-NMDA receptors in the lateral parabrachial nucleus modulate sodium appetite
    Juliana I F De Gobbi
    Department of Psychology, Cardiovascular Center, University of Iowa, Iowa City, 52242 1407, USA
    Brain Res 1301:44-51. 2009
    ..A possible interaction of serotonin with glutamate within the LPBN is discussed...
  4. pmc Mineralocorticoid receptor antagonism prevents hedonic deficits induced by a chronic sodium appetite
    Michael J Morris
    Department of Psychology, Integrative Physiology and Pharmacology, and the Cardiovascular Center, The University of Iowa, Iowa City, IA 52242 1407, USA
    Behav Neurosci 124:211-24. 2010
    ..We conclude that an unresolved sodium appetite will reduce responding for rewards and that experimental manipulations that reduce sodium appetite (e.g., access to saline or blockade of MR) decrease hedonic deficits...
  5. pmc Drinking and arterial blood pressure responses to ANG II in young and old rats
    Robert L Thunhorst
    Dept of Psychology, Univ of Iowa, 11 Seashore Hall E, Iowa City, IA 52242 1407, USA
    Am J Physiol Regul Integr Comp Physiol 299:R1135-41. 2010
    ..In summary, young rats appear to be more sensitive to the inhibitory effects of increased arterial blood pressure on water drinking than are older animals...
  6. pmc The brain Renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance
    Justin L Grobe
    Department of Internal Medicine, University of Iowa, Iowa City, 52242, USA
    Cell Metab 12:431-42. 2010
    ..adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure...
  7. pmc Central interactions of aldosterone and angiotensin II in aldosterone- and angiotensin II-induced hypertension
    Baojian Xue
    Department of Psychology, Cardiovascular Center, University of Iowa, 11 Seashore Hall E, Iowa City, IA 52242, USA
    Am J Physiol Heart Circ Physiol 300:H555-64. 2011
    ..The pressor effects produced by systemic ANG II or Aldo involve increased central ROS and sympathetic outflow...
  8. pmc Cancer induces inflammation and depressive-like behavior in the mouse: modulation by social housing
    Donald M Lamkin
    Department of Psychology, University of Iowa, IA, USA
    Brain Behav Immun 25:555-64. 2011
    ..It is concluded that tumor elicits anhedonic depressive-like behavior in a murine model of ovarian cancer. This may have important implications for etiology of depression in the clinical cancer setting...
  9. pmc Effects of β-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats
    Robert L Thunhorst
    Dept of Psychology, Univ of Iowa, 11 Seashore Hall E, Iowa City, IA 52242 1407, USA
    Am J Physiol Regul Integr Comp Physiol 300:R1001-8. 2011
    ..In conclusion, there are age-related differences in β-adrenergic receptor-mediated drinking that can be explained only in part by age-related differences in renin secretion after β-adrenergic receptor stimulation...
  10. pmc Behavioral cross-sensitization between DOCA-induced sodium appetite and cocaine-induced locomotor behavior
    Martin J Acerbo
    Departments of Psychology, Pharmacology, and Health and Human Physiology, and the Cardiovascular Center, The University of Iowa, Iowa City, IA 52242, USA
    Pharmacol Biochem Behav 98:440-8. 2011
    ..The underlying mechanisms accounting for this relationship may be the fact that psychostimulants and an unresolved craving for sodium can act as potent stressors...
  11. pmc Altered ADAR 2 equilibrium and 5HT(2C) R editing in the prefrontal cortex of ADAR 2 transgenic mice
    M Singh
    Department of Internal Medicine, University of Iowa, Iowa City, USA
    Genes Brain Behav 10:637-47. 2011
    ..These results altogether suggest that altered 5HT(2C) R function could be contributing to enhanced depression-like behavior of ADAR2 transgenic mice and further implicate ADAR2 as a contributing factor in cases of affective disorder...
  12. ncbi Opioid mechanisms that mediate the palatability of and appetite for salt in sodium replete and deficient states
    Elisa S Na
    Department of Psychology, The University of Iowa, Iowa City, IA 52242 1407, USA
    Physiol Behav 106:164-70. 2012
    ..The results indicate that endogenous opioids alter the processing of central information to affect hedonic mechanisms that influence behaviors related to sodium consumption and palatability...
  13. pmc Stress, depression and cardiovascular dysregulation: a review of neurobiological mechanisms and the integration of research from preclinical disease models
    Angela J Grippo
    Department of Psychiatry and Brain Body Center, University of Illinois at Chicago, Chicago, IL 60612, USA
    Stress 12:1-21. 2009
    ..This will ultimately promote the development of better treatments and interventions for individuals with co-morbid psychological and somatic pathologies...
  14. pmc Sex differences and central protective effect of 17beta-estradiol in the development of aldosterone/NaCl-induced hypertension
    Baojian Xue
    Dept of Psychology, Univ of Iowa, 11 Seashore Hall E, Iowa City, IA 52242, USA
    Am J Physiol Heart Circ Physiol 296:H1577-85. 2009
    ..Taken together, the results indicate that central estrogen plays a protective role in the development of Aldo/NaCl-induced hypertension and that this may result from reduced sympathetic outflow...
  15. pmc Affect-related behaviors in mice misexpressing the RNA editing enzyme ADAR2
    Minati Singh
    Department of Psychology, University of Iowa, Iowa City, IA 52242, USA
    Physiol Behav 97:446-54. 2009
    ..Taken together, the results suggest that ADAR2 transgenic mice represent a novel rodent model of endogenous behavioral despair and anxiety accompanied by elevated hypothalamo-pituitary adrenal axis activity...
  16. pmc Hypotension- and osmotically induced thirst in old Brown Norway rats
    Robert L Thunhorst
    Dept of Psychology, Univ of Iowa, 11 Seashore Hall E, Iowa City, IA 52242 1407, USA
    Am J Physiol Regul Integr Comp Physiol 297:R149-57. 2009
    ..Lastly, age-related declines in drinking appeared to be more severe in response to hypotension than in response to cellular dehydration...
  17. pmc Behavioral cross-sensitization between morphine-induced locomotion and sodium depletion-induced salt appetite
    Elisa S Na
    Department of Psychology, The University of Iowa, Iowa City, IA 52242 1407, United States
    Pharmacol Biochem Behav 93:368-74. 2009
    ....
  18. pmc Protective actions of estrogen on angiotensin II-induced hypertension: role of central nitric oxide
    Baojian Xue
    Department of Psychology, University of Iowa, 11 Seashore Hall E, Iowa City, IA 52242, USA
    Am J Physiol Heart Circ Physiol 297:H1638-46. 2009
    ....
  19. pmc Hindlimb unloading elicits anhedonia and sympathovagal imbalance
    Julia A Moffitt
    Department of Psychology, The University of Iowa, Iowa City, IA 52242 1407, USA
    J Appl Physiol (1985) 105:1049-59. 2008
    ..These findings further elucidate the pathophysiological link between cardiovascular diseases and affective disorders...
  20. pmc Right atrial stretch alters fore- and hind-brain expression of c-fos and inhibits the rapid onset of salt appetite
    Juliana Irani Fratucci De Gobbi
    Department of Psychology, University of Iowa, 11 Seashore Hall E, Iowa City, IA 52242 1407, USA
    J Physiol 586:3719-29. 2008
    ....
  21. pmc Salt craving: the psychobiology of pathogenic sodium intake
    Michael J Morris
    Department of Psychology, The University of Iowa, Iowa City, IA, 52242 1407, USA
    Physiol Behav 94:709-21. 2008
    ....
  22. ncbi The effects of chronic fluoxetine treatment on chronic mild stress-induced cardiovascular changes and anhedonia
    Angela J Grippo
    Department of Psychology, Cardiovascular Center, University of Iowa, Iowa City, Iowa 52242 1407, USA
    Biol Psychiatry 59:309-16. 2006
    ..Here we investigated the effects of a serotonin-specific reuptake inhibitor on a behavioral index of depression (anhedonia) and cardiac function in rats exposed to CMS...
  23. ncbi Role of nitrosyl factors in the hindlimb vasodilation elicited by baroreceptor afferent nerve stimulation
    Olga S Possas
    Department of Pharmacology, University of Iowa, 11 Seashore Hall E, Iowa City, Iowa 52242 1407, USA
    Am J Physiol Regul Integr Comp Physiol 290:R741-8. 2006
    ....
  24. ncbi Corticotropin-releasing hormone in the lateral parabrachial nucleus inhibits sodium appetite in rats
    Emilio de Castro e Silva
    Department of Physiology, Health Sciences Institute, Federal University of Bahia, Bahia, Brazil
    Am J Physiol Regul Integr Comp Physiol 290:R1136-41. 2006
    ..This mechanism may contribute to the behavioral control of restoration of body fluid homeostasis in sodium-deficient states...
  25. pmc Downregulation of propranolol-sensitive beta-adrenoceptor signaling after inhibition of nitric oxide synthesis
    Erin J Whalen
    Department of Pharmacology, University of Iowa, Iowa City, IA, USA
    Br J Pharmacol 147:755-64. 2006
    ....
  26. ncbi Thermoregulatory behavior is disrupted in rats with lesions of the anteroventral third ventricular area (AV3V)
    Douglas G Whyte
    Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA
    Physiol Behav 87:493-9. 2006
    ..These results demonstrate that the AV3V region is pivotal in the regulation of both autonomic and behavioral thermoregulatory effector mechanisms...
  27. ncbi Tachyphylaxis to 5-HT3-receptor-mediated activation of vagal afferents is prevented by co-activation of 5-HT2 receptors
    Patrick J Lacolley
    Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA
    Brain Res 1093:105-15. 2006
    ..These results suggest that the loss of response to 5-HT(3)R agonists is due to desensitization of 5-HT(3)Rs on vagal afferents mediating the BJR and that co-activation of 5-HT(2)Rs prevents the desensitization of these 5-HT(3)Rs...
  28. ncbi Lesions of the anteroventral third ventricle region exaggerate neuroendocrine and thermogenic but not behavioral responses to a novel environment
    Douglas G Whyte
    Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242 1407, USA
    Am J Physiol Regul Integr Comp Physiol 292:R137-42. 2007
    ..They also confirm that the physiological and hormonal components of the stress response are independent of certain behavioral measures of stress...
  29. ncbi Reduced hedonic behavior and altered cardiovascular function induced by mild sodium depletion in rats
    Angela J Grippo
    Department of Psychology and the Cardiovascular Center, University of Iowa, IA 52242 1407, USA
    Behav Neurosci 120:1133-43. 2006
    ..Thus, mild sodium depletion produces hypohedonia and cardiovascular alterations, which has implications for understanding behavioral and cardiovascular consequences of sodium deficiency...
  30. ncbi Sadness and broken hearts: neurohumoral mechanisms and co-morbidity of ischemic heart disease and psychological depression
    A K Johnson
    Department of Psychology, Cardiovascular Center, University of Iowa, Iowa City, IA 52242 1407, USA
    J Physiol Pharmacol 57:5-29. 2006
    ..The demonstrated validity of each of these models will be of great value in elucidating the nature of the actions and interactions of these humoral agents as they contribute to the co-morbid conditions of heart failure and depression...
  31. ncbi Hemodynamic responses elicited by gamma2-MSH or blood replacement in hemorrhaged rats
    Erin J Whalen
    Department of Psychology, University of Iowa, Iowa City, Iowa 52242, USA
    J Surg Res 139:121-7. 2007
    ..Systemic injections of compounds such as gamma(2)-melanocyte-stimulating hormone (gamma(2)-MSH), which increase sympathetic neurogenic vasoconstriction, may be beneficial in treating hemorrhage-induced hypotension...
  32. ncbi 5-HT2 and 5-HT3 receptors in the lateral parabrachial nucleus mediate opposite effects on sodium intake
    J I F De Gobbi
    Department of Physiology, Bioscience Institute, Paulista State University UNESP, Distrito de Rubiao Junior, S N, 18618 000 Botucatu, SP, Brazil
    Neuroscience 146:1453-61. 2007
    ..The results provide new information concerning the control of sodium intake by LPBN mechanisms...
  33. ncbi Sex differences in angiotensin II- induced hypertension
    B Xue
    Department of Psychology, University of Iowa, Gainesville, IA 52242, USA
    Braz J Med Biol Res 40:727-34. 2007
    ..Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension...
  34. ncbi Dorsal raphe nuclei integrate allostatic information evoked by depletion-induced sodium ingestion
    Daniel Badauê-Passos
    Departmento de Fisiologia, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Brazil
    Exp Neurol 206:86-94. 2007
    ..Projections from the LT cells may contribute to inhibitory mechanisms involving 5-HT neurons in the DRN that limit the intake of sodium and prevent excess volume expansion...
  35. pmc Glucocorticoids increase salt appetite by promoting water and sodium excretion
    Robert L Thunhorst
    Department of Psychology, University of Iowa, 11 Seashore Hall E, Iowa City, IA 52242 1407, USA
    Am J Physiol Regul Integr Comp Physiol 293:R1444-51. 2007
    ..We conclude that increased urinary excretion, especially of water, during glucocorticoid treatment may explain the increased ingestion of water and sodium that occurs during coadministration with mineralocorticoids...
  36. ncbi The sensory psychobiology of thirst and salt appetite
    Alan Kim Johnson
    Department of Psychology, University of Iowa, Iowa City, IA 52242 1407, USA
    Med Sci Sports Exerc 39:1388-400. 2007
    ..This information is important for appreciating the extent to which thirst and sodium appetite motivational states and behaviors can be relied on to maintain and repair disruptions of body fluid homeostasis...
  37. pmc The neural substrates of enhanced salt appetite after repeated sodium depletions
    Elisa S Na
    Department of Psychology, The University of Iowa, Iowa City, IA 52242, USA
    Brain Res 1171:104-10. 2007
    ..Experience with sodium depletion enhances its ingestion and may have a direct impact on central structures implicated in sodium appetite and reward signaling...
  38. ncbi Water intake during the development of renal hypertension (2K-1C) in mice
    Claudia M Santos
    Department of Psychology, University of Iowa, Iowa City, IA 52242, USA
    Physiol Behav 85:512-6. 2005
    ..8% saline intake between any of the pairs of groups. In summary, the reduction of blood flow to a single kidney in the 2K-1C model of renal hypertension induces high blood pressure accompanied by sustained hyperdipsia in the mouse...