Neural basis of learned food aversion and nausea

Summary

Principal Investigator: CHARLES HORN
Abstract: Some medications produce nausea and vomiting that may lead to loss of appetite and reduced food intake, which can negatively affect recovery from disease. Nausea and vomiting are frequently observed with use of cytotoxic chemotherapy agents. Little is known about the neural pathways and mechanism for detecting toxins. Gastrointestinal (GI) sensory nerve fibers play an important role in the initiation of vomiting, and may also be involved in the stimulation of nausea. The present proposal will focus on identifying the pathways and neurochemistry of GI vagal and spinal afferent fibers and brain nuclei that are activated by toxins. To address this issue experiments will be conducted to examine the effects of cisplatin (a chemotherapy agent) and lithium chloride (LiCI) (treatments that produce nausea in humans) on visceral afferent nerve activity and brain and spinal cord Fos expression. Studies will determine: (1) the properties (neurotransmitter receptors, stretch-sensitivity, site of innervation in the stomach and intestine) of vagal and spinal afferent fibers responsive to cisplatin and LiCI using a novel application of single-unit neurophysiology, (2) the brainstem and spinal cord sites that are activated by cisplatin and LiCI treatment using Fos expression, (3) the peripheral neural pathways involved in brain Fos expression produced by cisplatin and LiCI using lesions of the vagus and GI spinal nerves, and (4) the neurotransmitter receptors that play a role in the brain Fos response produced by cisplatin and LiCI treatment. An understanding of the physiology of toxin detection may contribute to nausea treatment in a large number of clinical situations, including cancer chemotherapy, diabetic gastroparesis, anorexia nervosa, ischemic gastropathy, chronic intestinal obstruction, abdominal malignancy, and functional dyspepsia. Effective treatment of nausea may substantially improve the quality of life for patients with chronic disease.
Funding Period: 2009-09-25 - 2010-08-31
more information: NIH RePORT

Top Publications

  1. pmc Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews
    Charles C Horn
    Biobehavioral Medicine in Oncology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
    Am J Physiol Regul Integr Comp Physiol 306:R341-51. 2014
  2. pmc Why can't rodents vomit? A comparative behavioral, anatomical, and physiological study
    Charles C Horn
    Biobehavioral Medicine in Oncology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 8:e60537. 2013
  3. ncbi Effects of gastric distension and infusion of umami and bitter taste stimuli on vagal afferent activity
    Charles C Horn
    Monell Chemical Senses Center, Philadelphia, PA 19104, USA
    Brain Res 1419:53-60. 2011
  4. pmc Behavioral patterns associated with chemotherapy-induced emesis: a potential signature for nausea in musk shrews
    Charles C Horn
    Biobehavioral Medicine in Oncology Program, University of Pittsburgh Cancer Institute Pittsburgh, PA, USA
    Front Neurosci 5:88. 2011
  5. pmc Computerized detection and analysis of cancer chemotherapy-induced emesis in a small animal model, musk shrew
    Dong Huang
    Carnegie Mellon University, Robotics Institute, Pittsburgh, PA, USA
    J Neurosci Methods 197:249-58. 2011
  6. pmc Food restriction, refeeding, and gastric fill fail to affect emesis in musk shrews
    Charles C Horn
    Univ of Pittsburgh Cancer Institute, Hillman Cancer Center Research Pavilion, G 17b, Biobehavioral Medicine Program, 5117 Centre Ave, Pittsburgh, PA 15213, USA
    Am J Physiol Gastrointest Liver Physiol 298:G25-30. 2010
  7. pmc Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat
    Charles C Horn
    Monell Chemical Senses Center, Philadelphia, Pennsylvania 15213, USA
    Am J Physiol Regul Integr Comp Physiol 297:R1375-82. 2009
  8. ncbi Electrophysiology of vagal afferents: amino acid detection in the gut
    Charles C Horn
    Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA
    Ann N Y Acad Sci 1170:69-76. 2009
  9. pmc Pica as an adaptive response: Kaolin consumption helps rats recover from chemotherapy-induced illness
    Bart C De Jonghe
    Monell Chemical Senses Center, 3500 Market St, Philadelphia, PA 19104, USA
    Physiol Behav 97:87-90. 2009
  10. pmc Brain Fos expression induced by the chemotherapy agent cisplatin in the rat is partially dependent on an intact abdominal vagus
    Charles C Horn
    Monell Chemical Senses Center, Philadelphia, PA 19104, USA
    Auton Neurosci 148:76-82. 2009

Scientific Experts

  • Charles C Horn
  • Paul L R Andrews
  • Bart C De Jonghe
  • Dong Huang
  • Nadia E García-Medina
  • Fernando de la Torre
  • Severine Henry
  • Kelly Meyers
  • Maureen P Lawler
  • Michael G Tordoff
  • Luz M Martínez
  • María E Jiménez-Capdeville
  • Juan M Delgado
  • Marc Ciucci

Detail Information

Publications18

  1. pmc Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews
    Charles C Horn
    Biobehavioral Medicine in Oncology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
    Am J Physiol Regul Integr Comp Physiol 306:R341-51. 2014
    ..Furthermore, the current neural tracing data suggest brain stem anatomical circuits that are activated by GI signaling in the musk shrew. ..
  2. pmc Why can't rodents vomit? A comparative behavioral, anatomical, and physiological study
    Charles C Horn
    Biobehavioral Medicine in Oncology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 8:e60537. 2013
    ..The implications of these findings for the utility of rodents as models in the area of emesis research are discussed...
  3. ncbi Effects of gastric distension and infusion of umami and bitter taste stimuli on vagal afferent activity
    Charles C Horn
    Monell Chemical Senses Center, Philadelphia, PA 19104, USA
    Brain Res 1419:53-60. 2011
    ..The current results suggest that sensitivity to umami or bitter stimuli is not a common property of gastric vagal afferent fibers...
  4. pmc Behavioral patterns associated with chemotherapy-induced emesis: a potential signature for nausea in musk shrews
    Charles C Horn
    Biobehavioral Medicine in Oncology Program, University of Pittsburgh Cancer Institute Pittsburgh, PA, USA
    Front Neurosci 5:88. 2011
    ....
  5. pmc Computerized detection and analysis of cancer chemotherapy-induced emesis in a small animal model, musk shrew
    Dong Huang
    Carnegie Mellon University, Robotics Institute, Pittsburgh, PA, USA
    J Neurosci Methods 197:249-58. 2011
    ..These results also yield a better understanding of the brain's central pattern generator for emesis and indicate that the retching response in the musk shrew (at ∼5.4 Hz) is the fastest ever recorded in a free-moving animal...
  6. pmc Food restriction, refeeding, and gastric fill fail to affect emesis in musk shrews
    Charles C Horn
    Univ of Pittsburgh Cancer Institute, Hillman Cancer Center Research Pavilion, G 17b, Biobehavioral Medicine Program, 5117 Centre Ave, Pittsburgh, PA 15213, USA
    Am J Physiol Gastrointest Liver Physiol 298:G25-30. 2010
    ..These results may have implications for how we treat patients who experience a constellation of side effects, including nausea and emesis, since stimulating appetite may not necessarily inhibit emetic pathways...
  7. pmc Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat
    Charles C Horn
    Monell Chemical Senses Center, Philadelphia, Pennsylvania 15213, USA
    Am J Physiol Regul Integr Comp Physiol 297:R1375-82. 2009
    ..These data suggest that lPBN-lesioned animals not only demonstrate pica after cisplatin treatment, but, in fact, show an exaggerated response that is greatly in excess of any treatment known to produce kaolin intake in rats...
  8. ncbi Electrophysiology of vagal afferents: amino acid detection in the gut
    Charles C Horn
    Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA
    Ann N Y Acad Sci 1170:69-76. 2009
    ..Several problems with recording the electrophysiological signals of vagal afferents are discussed, with particular reference to sampling the afferent signals from the duodenum and liver region...
  9. pmc Pica as an adaptive response: Kaolin consumption helps rats recover from chemotherapy-induced illness
    Bart C De Jonghe
    Monell Chemical Senses Center, 3500 Market St, Philadelphia, PA 19104, USA
    Physiol Behav 97:87-90. 2009
    ..Thus, clay consumption appeared beneficial in that it either protected the rats from illness or enhanced recovery and might prove useful as an adjunct therapy for other animals, including humans, experiencing visceral malaise...
  10. pmc Brain Fos expression induced by the chemotherapy agent cisplatin in the rat is partially dependent on an intact abdominal vagus
    Charles C Horn
    Monell Chemical Senses Center, Philadelphia, PA 19104, USA
    Auton Neurosci 148:76-82. 2009
    ..These results suggest that a defined portion of cisplatin-induced Fos expression is dependent on vagal input, with a majority of this response determined by either direct action of cisplatin or humoral factors on the CNS...
  11. pmc Chemotherapy agent cisplatin induces 48-h Fos expression in the brain of a vomiting species, the house musk shrew (Suncus murinus)
    Bart C De Jonghe
    Monell Chemical Senses Ctr, Philadelphia, PA 19104, USA
    Am J Physiol Regul Integr Comp Physiol 296:R902-11. 2009
    ..Our findings suggest the existence of an extensive neural system that could be targeted to reduce nausea, vomiting, and malaise in cancer patients receiving chemotherapy...
  12. ncbi Chemotherapy-induced pica and anorexia are reduced by common hepatic branch vagotomy in the rat
    Bart C De Jonghe
    Monell Chemical Senses Center, 3500 Market St, Philadelphia, PA 19104, USA
    Am J Physiol Regul Integr Comp Physiol 294:R756-65. 2008
    ..This investigation contributes to the delineation of the physiology of pica and neural systems involved in malaise in the nonvomiting rat...
  13. pmc Why is the neurobiology of nausea and vomiting so important?
    Charles C Horn
    Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA
    Appetite 50:430-4. 2008
    ..A neurophysiological analysis of brain pathways provides an opportunity to more closely determine the neurobiology of nausea and vomiting and its prodromal signs (e.g., cold sweating, salivation)...
  14. pmc Conditioned flavor aversion and brain Fos expression following exposure to arsenic
    Nadia E García-Medina
    Departamento de Bioquimica, Facultad de Medicina, Universidad Autonoma de San Luis Potosi, Av V Carranza 2405, San Luis Potosi 78210, SLP, Mexico
    Toxicology 235:73-82. 2007
    ..1 mg/kg body weight. In summary, these data indicate that arsenic given by oral administration is detected by the brain in low concentrations, and activates specific nuclei, which might trigger behavioral responses, such as CFA...
  15. pmc Brain Fos expression during 48 h after cisplatin treatment: neural pathways for acute and delayed visceral sickness
    Charles C Horn
    Monell Chemical Senses Center, 3500 Market Street, Philadephia, PA 19104, USA
    Auton Neurosci 132:44-51. 2007
    ..These results indicate that cisplatin activates a neural system that includes the dorsal vagal complex (NTS and AP), CeA, and BNST...
  16. pmc Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases
    Paul L R Andrews
    Division of Basic Medical Sciences, St George s University of London, Cranmer Terrace, London, SW 17 0RE, UK
    Auton Neurosci 125:100-15. 2006
    ....
  17. pmc Thoracic cross-over pathways of the rat vagal trunks
    Charles C Horn
    Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA
    Brain Res 1060:153-61. 2005
    ....