13. MOTIVATION Flashcards
Define motivation
- Motivation refers to the driving force of physical need to do something
When does anabolism & catabolism occur in regards to feeding?
- Metabolism is a combination of both anabolism & catabolism
- Anabolism occurs during the prandial state (eating), where excess glucose, fatty acids are stored
- Catabolism occurs during the post-prandial state (after eating) where the trigylceride, glycogen stores etc. are broken down
What is the parabiosis experiment of mice?
- Parabiosis = fusion
- An obese mice with a defect in the ob gene (ob/ob), so it was unable to produce leptin
- This obese mice was fused to a normal mice, so that their circulation was shared
- Researchers found the obese mouse lost weight & it’s weight matched that of the control mouse
- The leptin from the normal mouse entered the circulation of the ob/ob mouse & acted on leptin receptors to regulate feeding
What is a satiety signal involved in the long term hormonal regulation of feeding?
- Leptin is involved in the long-term hormonal regulation of feeding
What is leptin?
- Leptin is satiety signal
- It is released by adipose tissue, when fat stores are replenished to regulate feeding
- High levels of leptin -> full, inhibits feeding
Where are leptin receptors?
- Leptin is released from adipose tissue & acts on the leptin receptor
- The leptin receptor is located in the arcuate nucleus
What does a lesion of the lateral hypothalamus cause?
- LATERAL HYPOTHALMUS = lose weight (anorexia), decreased appetite
- Results in lateral hypothalamic syndrome
What does a lesion of the ventromedial hypothalamus cause?
- VENTROMEDIAL HYPOTHALAMUS = obesity/weight gain, increased appetite
- Results in ventromedial hypothalamic syndrome
What are anorectic peptides?
- Anorectic peptides SUPPRESS appetite, inhibit feeding
- Endogenous neuropeptides such as alpha-MSH or CART
What are orexigenic peptides?
- OREXIGENIC peptides INCREASE appetite, stimulate feeding
- Endogenous peptides such as AgRP, NPY, orexin, MCH, Ghrelin
What two anorectic peptides are released in response to high leptin?
- Alpha-MSH (Alpha - melanocyte stimulating hormone)
2. CART (Cocaine-amphetamine regulated transcript)
Where are alpha MSH & CART released from?
- Alpha- MSH & CART are released from alpha-MSH & CART neurones in the arcuate nucleus
Where do alpha MSH & CART neurones project to & how do they inhibit feeding?
- LATERAL HYPTHALAMIC AREA - inhibit feeding
- PARAVENTRICULAR NUCLEUS - stimulates neurones which release ACTH & TSH from anterior pituitary to increase metabollic rate
- BRAIN STEM - stimulate sympathetic activity
What is the response to high leptin called?
- Anorexic response
- Aims to inhibit feeding
What is the response to low leptin called?
- Orexigenic response
- Aims to increase feeding
What are two orexigenic peptides released in response to low leptin?
- AgRP (agouti-related peptide)
- NPY (Neuropeptide Y)
- Stimulate appetite
Where are AgRP & NPY released from?
- AgRP & NPY are released by arcuate AgRP & NPY neurones in the arcuate nucleus
How are leptin levels detected?
- Leptin receptors are in the arcuate nucleus
- High or low levels of leptin will be detected by the arcuate nucleus
- Either anorectic or orexigenic peptides will be released by arcuate neurones (AgRP, NPY, CART or alpha MSH)
Where do the AgRP & NPY neurones project to & how do they stimulate feeding?
- LATERAL HYPOTHALAMIC AREA - stimulate feeding
- PARAVENTRICULAR AREA - inhibits neurones which cause release of ACTH & TSH by anterior pituitary to decrease basal metabolic rate
- BRAIN STEM - inhibit sympathetic activity & stimulate parasympathetic activity
How do projection of AgRP & NPY to the lateral hypothalamus stimulate feeding?
- The arcuate AgRP & NPY neurones project to the lateral hypothalamus to stimulate feeding
- The lateral hypothalamus produces orexigenic peptides to stimulate appetite:
1. OREXIN
2. MELANIN CONCENTRATING HORMONE
Where are orexin & MCH released from & what do they do?
- Orexin & MCH are released from the lateral hypothalamus
- They are orexigenic peptides
- Orexin = promotes meal initiation
- MCH = prolongs consumption of food
What two competitive peptides bind to MC4 receptor?
- alpha MSH
- AgRP
- Both bind to MC4 and have opposite effects
Where are MC4 receptors located?
- Hypothalamic neurones
What’s the effect of alpha MSH binding to the MC4 receptor?
- alpha-MSH is an agonist for MC4 receptor
- Binding of alpha-MSH inhibits feeding
What’s the effect of AgRP binding to the MC4 receptor?
- AgRP is a competitive antagonist for the MC4 receptor
- Binding to teh MC4 receptor counteracts the effects of alpha-MSH to stimulate appetite rather than inhibit it
Which peptides bind to the MC4 receptor at high & low levels of leptin?
- High leptin = alpha MSH released & binds to MC4 -> inhibits feeding
- Low leptin = AgRP released & binds to MC4 -> stimulates feeding
Define satiety
- Satiety is the feeling of fullness & the suppression of food consumption after a meal for a long period
What are the three phases of feeding/digestion?
- CEPHALIC PHASE
- GASTRIC PHASE
- INTESTINAL PHASE
What happens in the cephalic phase?
- Cephalic phase is the phase in anticipation to a meal
- Increased saliva secretion
- Ghrelin released from empty stomach
- Activation of AgRP & NPY neurones in arcuate nucleus
- Parasympathetic nervous system & enteric nervous system activation
What happens in the gastric phase?
- The phase during food consumption
- Release of mucin & digestive secretions in response to chewing or swallowing
- Gastric distension of stomach
What happens in the intestinal phase?
- Food is transported from distended stomach to intestines for intestinal phase
- Cholecystokinin released in response to fatty foods by the intestine
What are three satiety signals in the short term regulation of feeding?
- GASTRIC DISTENSION
- CCK (Cholecystokinin)
- INSULIN
How does gastric distension act as a short term satiety signal?
- Gastric distension signals to the nucleus solitarius tract (NTS) via the vagus nerve to inhibit feeding
How does cholecystokinin act as a short term satiety signal?
- CCK acts on vagus nerve to inhibit feeding
How does insulin act as a short term satiety signal?
- Insulin is released by the beta cells of the pancreas
- It’s released in response to excess circulating glucose
- It acts on the arcuate nucleus to induce satiety
How is dopamine involved in feeding behaviour?
- Dopaminergic neurones are involved in releasing dopamine, to cause the wanting fro food
- Dopamine involved in motivation but not liking (not involved in hedonic aspect)
- Mesolimbic pathway - dopaminergic neurones project from the VTA to nucleus accumbens
What is positive & negative reinforcement?
- Positive reinforcement - repeating a behaviour due to pleasant or rewarding effect
- Negative reinforcement - repeating a behaviour to avoid an unpleasant experience
What’s the link between dopamine & positive reinforcement?
- Release of dopamine in the nucleus accumbens is thought to drive positive reinforcement behaviour
- However, dopamine is only involved in the motivational aspect not the hedonic aspect (not involved in liking)
What’s the link between dopamine & negative reinforcement?
- Suppression of the mesolimbic pathway is associated with negative reinforcement
How is positive & negative reinforcement involved in addiction?
- Release of dopamine in nucleus accumbens drives the addiction = POSITIVE REINFORCEMENT
- However, dependence on the source of addiction can lead to withdrawal effects when stopped.
- Individuals continue to use substance or source of addiction to avoid the unpleasant effects of withdrwal = NEGATIVE REINFORCEMENT
- In addicted individuals, the drugs are thought to act on amygdala not GABAergic neurones
What happens to D2 receptors in individuals suffering from obesity or addiction?
- There’s a downregulation of D2 receptor expression
- Decrease in D2 receptors is correlated with increased craving & a vulnerability to relapse
- Rewarding effects are reduced, so individuals need to increase the dosage
What happens to D2 receptors in individuals with depression?
- There’s a downregulation of D2 receptors in individuals with depression
- Leads to decreased interest in activities that would normally be rewarding
How is serotonin involved in feeding behaviour?
- Serotonin is released in the hypothalamus in anticipation to a meal & spikes during a meal
- Low serotonin levels are associated with anorexia nervosa, bullimia & depression. Co-morbidity with these disorders
