Complex brain function: reward

Question 1

LO and Lecture outline

Answer 1

LO

• Describe the different components of reward: hedonic vs motivation
• Describe which structures of the brain are involved in the rewarding effects of food
• Describe the neural substrates that have been identified in the different components of reward

Lecture outline

• Introduction to pleasure, food reward and feeding behavior
• Eating disorders
• Key structures of the brain that co-ordinate feeding homeostatic circuits vs reward circuits
• Neural substrates of hedonic and motivational aspects of food reward
• Insight to eating disorders

Question 2

Pleasure and behaviour

Answer 2

‘‘We recognize pleasure as the first good innate in us, and from pleasure we begin every act of choice and avoidance, and to pleasure we return again, using the feeling as the standard by which we judge every good.” – Epicurus

Question 3

What does eating serve as an essential role in?

Answer 3

Survival and homeostasis

Question 4

What can food intake be influenced by?

Answer 4

Food intake can be influenced by the pleasurable effects of food

Question 5

What is the pleasure of eating food generate by?

Answer 5

The pleasure of eating food is generated by a ‘liking’ reaction in the brain

Question 6

‘Liking’ circuits are also called what?

Answer 6

‘Hedonic’ circuits

Question 7

Tell me about Hedonic feeding

Answer 7

Hedonic feeding is not driven by a metabolic need

Hedonic or ‘liking’ systems are a component of reward

Question 8

What sort of things are included under the term eating disorders?

Answer 8

Eating disorders can include obesity, bulimia and anorexia

Question 9

How has the number of severely obese and obese children changed over the last 10 years?

Answer 9

The number of severely obese and obese children has increased and almost doubled in the last ~10 years

Question 10

What underpins the potential for therapeutics with feeding?

Answer 10

Neural mechanisms and circuitry that underpin the reward of feeding behaviour has potential for novel therapeutics

Question 11

Brain systems controlling food intake and feeding

Homeostatic system

Tell me about the Orexigenic and Anorexigenic neurons

Answer 11

Orexigenic= appetite increase

Anorexigenic= appetite suppressing

Question 12

Who identified reward centers existed in the brain of rodents and what did this approach become known as?

Answer 12

Olds and Milner (1954) identified reward centers existed in the brain of rodents

This approach became known as brain stimulation reward

Question 13

Tell me how what was done during the development of the brain stimulation reward?

Answer 13

• Different positioning of the electrode allowed further mapping of the brain circuitry of reward
• The reward system is the neural network that receives and evaluates the rewarding properties of stimuli
• The network consists of multiple interacting neural circuits.
• Robust self-stimulation behaviour is obtained with electrodes along the medial forebrain bundle (MFB)

Question 14

Self-stimulation is observed from electrodes located in several brain areas, including what?

Answer 14

• Nucleus Accumbens (NAcc)
• Lateral hypothalamus (LH)
• Ventral Tegmental Area (VTA)
• Cortical structures

Question 15

Tell me some of the key structures of the reward circuit

Answer 15

Question 16

What did Berridge et al 2020 identify?

Answer 16

Berridge et al 2020: Affective orofacial liking reactions can be quantified to provide a readout for how much the subject likes a substance; food

Information from animal studies gives us the opportunity to learn more about reward in humans via facial expressions for example

Question 17

What are endogenous opioids and give some examples

Answer 17

Endogenous opioids are neuropeptides and include: enkephalins, dynorphins and endorphins

Question 18

Tell me 3 opioid receptor subtypes

Answer 18

3 opioid receptor subtypes: mu, kappa and delta

Question 19

What types of receptors are opioid receptors?

Answer 19

G-protein coupled receptors

Question 20

What can opioid receptors be activated by?

Provide examples

Answer 20

Can be activated by Agonists which include morphine and heroin, Antagonist: Naloxone

Question 21

What molecules are endogenous endocannabinoids and provide some examples?

Answer 21

Endogenous endocannabinoids are lipid molecules: anandamide and 2-arachidonoylglycerol (2-AG)

Question 22

Name 2 cannabinoid receptor subtypes?

Answer 22

CB1 and CB2

Question 23

What type of receptors are cannabinoid receptors?

Answer 23

GPCR

Question 24

What is the CB1 subtype predominantly express in?

Answer 24

CB1 subtype is predominantly expressed in the central nervous system

Question 25

Name an cannabinoid agonist?

Answer 25

Agonists include the drug THC (this is a component of marijuana)

Question 26

Tell me the effect of Morphine and Naloxone?

Answer 26

Morphine enhances ‘liking’ responses of rats for palatable foods

Naloxone decreases food intake in rats, especially when sucrose is used

Question 27

Injection of opioid receptor agonist (DAMGO) and measuring of facial ‘liking’ reaction identified what?

Answer 27

• Role for mu opioid receptors
• Precise map of the nucleus accumbens
• Hedonic hotspot (10% of Nacc)
• A larger region for food intake (‘wanting’)

Question 28

Hedonic hotspots of the brain

Answer 28

Question 29

Hedonic hotspots are functionally connected

Answer 29

Question 30

What is the active ingredient of cannabis?

What effect does it have?

Answer 30

Anecdotal evidence: the active ingredient of cannabis, 9-tetrahydrocannabinol increases food intake, particularly sugary foods.

Question 31

What does targeted injection of anandamide into the NAcc increase?

Answer 31

Targeted injection of anandamide into the NAcc increases facial liking expressions to sucrose

Question 32

There is an endocannabinoid hotspot in the NAcc that overlaps with what?

Answer 32

The opioid hotspot

Question 33

What has CB1 been co-localising with and what do they function to do?

Answer 33

CB1 receptors and mu receptors have been identified as co-localizing in neurones of the nucleus accumbens

Function together to co-ordinate the release of neurotransmitters

Question 34

What are the neural substrates of the ‘wanting’ aspects of reward?

Answer 34

Dopamine established as a key neurotransmitter in reward: Olds and Milner

Question 35

Hypothesis: dopamine signals reward ‘pleasure’

Answer 35

Hypothesis: dopamine signals reward ‘pleasure’

This hypothesis was tested using the facial expression paradigm combined with neurochemical lesions in the brain to reduce dopamine signaling

depletion of dopamine did not affect orofacial expression of liking in response to sweetness

BUT: reducing dopamine feeding did make rats aphagic

New hypothesis: Dopamine is required for ‘wanting’ motivational aspects of food reward

Question 36

Summary

Answer 36

• Dopaminergic pathways generate ‘wanting’ (incentive salience)
• The ‘wanting’ circuit is larger than the hedonic hotspot network
• ‘This network can generate intense incentive motivation without enhancing hedonic ‘liking’
• The ‘Liking’ circuits are composed of interconnected ‘hotspots’ (white in diagram)
• Signalling in one ‘hotspot’ can recruit other ‘hotspots’ to enhance ‘liking’ reactions.
• Disruption to one ‘hotspot’ can disrupt the recruitment of other ‘hotspots’