Chapter 11: Ingestive Behavior: Drinking
Lecture Outline
Homeostasis
Fluid Balance
Drinking and Salt Appetite
Osmometric thirst
Volumetric thirst
Neural Mechanisms of Thirst and Salt Appetite
Homeostasis
Homeostasis: "Change in the face of change so as to remain unchanged…"
Process of maintaining a constant internal environment
Assumes regulatory mechanisms:
System variable
Set-point
Detector
Correctional mechanism
Thirst
Thirst: tendency to seek and ingest water
Issues to consider:
Stimuli for thirst
Cellular dehydration
Volume changes
Hormonal involvement in thirst?
Neural circuits that mediate thirst?
Fluid Balance
Water Movement Across Compartments
Kidneys and Water/Salt Balance
Nephrons of the kidneys control excretion of:
Water
Kidneys excrete little water during fluid loss
Increased vasopressin release increases water retention
Salt
Kidneys excrete little salt during salt deficit
Increased aldosterone levels results in salt retention
Osmometric Thirst
Stimulus: increased tonicity of the interstitial fluid
Loss of fluid during evaporation
Ingestion of salt will increase tonicity and induce movement of water out of cells
Fitzsimons experiment: remove rat kidneys, inject various salts: measure water consumption.
Only substances that withdrew intracellular water (without crossing cell membrane) induced thirst (e.g. NaCl)
CNS Mediation of Osmometric Thirst
Osmoreceptors are in brain:
Infusions of NaCl into brain induce thirst
Brain tissue surrounding the anterior aspects of the 3rd ventricle may contain osmoreceptors
OVLT is candidate site for osmoreceptors
Located on blood side of BBB (near AV3V)
NaCl infused into the AV3V produces drinking
Lesions of the OVLT reduce osmometric thirst
Damage to the region near the AV3V in humans produces lack of thirst
Diagram of Osmometric Thirst
Hypovolemic Thirst
Reduced blood volume provokes drinking
Stimuli:
Blood loss
Loss of isotonic fluid (vomiting, diarrhea)
Experimental techniques
Injection of a colloid such as polyethylene glycol
- Sequesters water and salt: withdrawn from body
Hypovolemic stimuli produce:
Drinking
Salt appetite
Dual Hypovolemic Thirst Mechanisms
Angiotensin II is formed when blood flow through kidneys is reduced
AII has dual effects
Stimulates drinking
Produces an appetite for salt
Baroreceptors within atrium of heart signal blood volume:
Reduced stretch results in drinking
CNS Mediation of Hypovolemic Thirst
Subfornical organ (SFO) is site of action for angiotensin
Infusions of AII into SFO elicit drinking
Lesions of the SFO abolish drinking to AII
SFO projects to the median preoptic nuc
Atrial baroreceptors send signals to the NST
Projects from NST to AV3V region
AV3V projects to the med preoptic nuc
Summary of Dual Thirst Mechanisms
Eating and Body Weight
Metabolism
Initiation of Eating
Termination of Eating
Neural Control of Eating
Therapies for Obesity
Feeding
Appetitive (animals seek food)
Consummatory (animals consume food)
Biting, chewing
Sucking
Swallowing
Feeding serves to obtain and store energy
Glycogen (short-term)
Triglyceride (long-term)
The Fasting and Absorptive Phases of Metabolism
Feeding Terms
Hunger
Factors that start a meal
Satiety
Factors that stop a meal
Not illness
Anorexia
The notion of brain "Centers"
Feeding Initiation:
Environmental factors
Stress
Environmental cues (conditioned eating)
Taste of food
Presence of others (meal size goes up with group size)
Feeding Initiation:
Short-Term Hunger Signals
Glucoprivation
Fall in blood glucose stimulates hunger
Insulin, 2-DG induce glucoprivation and feeding
Lipoprivation
Interference with lipid metabolism induces eating
Methyl palmoxirate (MP)
Mercaptoacetate (MA)
Feeding Initiation: Blood Glucose
Blood glucose (notion of glucoreceptor)
Sensors for glucose utilization
Campfield: feeding associated with transient decline in BG
Location of Glucoreceptors?
Liver (may respond to both gluco- and lipoprivic)
Liver contains glucoreceptors that report to brain via vagus nerve
Infusions of 2-DG into hepatic portal vein produce immediate eating
Brain (uses only glucose for fuel)
Infusions of 5-TG into fourth ventricle
Block glucose metabolism and induce eating
Feeding Termination:
Short-term Factors
Head factors
Sham-feeding studies suggest minimal impact of head factors on ending a meal
Taste factors play a role in sensory-specific satiety
Gastric factors
Distension
Nutrient receptors monitor calories in stomach
Feeding Termination:
Short-term Factors continued
Intestinal factors
Food infusion into the duodenum suppresses sham-feeding in the rat
CCK: a putative satiety hormone
Released by entry of food into the duodenum
Controls rate of stomach emptying
Acts peripherally
CCK antagonists increase feeding
Feeding Control: The Liver
Feeding Termination:
Long-term Factors
Body weight is a determinant of food intake
Force-feeding studies: food intake falls as body weight increases
Koopman’s parabiotic rats
Intestinal systems were surgically connected
Donor rat overate, recipient underate
Leptin: a protein produced by fat that suppresses food intake and stimulates metabolism
Neural Organization of Feeding
Brainstem circuitry can control feeding in the absence of the forebrain
Decerebrate rats can lick, chew, and swallow
Lipoprivic and glucoprivic signals in the AP/NST
Taste information reaches the brainstem: the AP/NST
The NST in turn projects to the lateral parabrachial nuc.
Hypothalamic Regions Involved in Control of Feeding
PVN Influences on Feeding
PVN acts to inhibit feeding
PVN lesions produce overeating
Norepinephrine in the PVN increases feeding
Via activation of a2-adrenoceptors in the PVN
- Alpha2 agonists stimulate feeding
- Alpha2-antagonists suppress feeding
PVN cells are excited by a1-adrenergic agonists
e.g. Phenylpropanolamine, methoxamine
These drugs suppress feeding
Other PVN Factors That Modulate Feeding
5-HT in the PVN suppresses feeding
Agonists reduce feeding of carbohydrates
5-HT antagonists increase feeding
NPY: ravenous eating (maybe LH)
Galanin: Selectively stimulates consumption of fat
Issues for Rational Therapies for Obesity
Food intake and metabolism are controlled on multiple levels
Intervention on one level may result in compensation on another level
e.g. Subjects who overeat and stretch their stomach after stapling procedure
Obesity is a multi-factorial disorder
One therapy may not fit all
Obesity is a long-term disorder: requires long-term treatments
Examples of Obesity Treatments
Gastric stapling
Pharmacological:
Suppression of appetite (fenfluramine)
Cardiac problems with fenfluramine?
Stimulation of metabolism (ephedrine)
Blockade of fat formation: (hydroxycitrate)
Leptin:
Obese persons have normal levels of leptin?