Appetite and Addiction

PART 1 — Appetite

Learning Outcomes

  • Describe neuroendocrine control of body weight, hunger, and satiety.

  • Understand how disruptions to these systems can lead to obesity.

1. Body Image, Eating Disorders & Obesity

Links to Mental Health

Studies (e.g., Thompson et al., Peto, Brausch & Muehlenkamp) show:

  • Body dissatisfaction is common and predicts eating disorders.

  • Exposure to unrealistic beauty ideals increases risk.

Obesity & Bullying

  • Overweight adolescents are more likely to be bullied (Eisenberg et al., Falkner et al.).

  • This contributes to low self-esteem and disordered eating.

Obesity & Health

  • Increased risk of diabetes, cardiovascular disease, and metabolic disorders (Van den Berg & Neumark-Sztainer).

2. Ingestive Behaviour

Humans regulate:

  • Fluid balance (water & sodium chloride)

  • Eating behaviour (macronutrients & micronutrients)

Metabolic Basics

  • Food → Rise in blood glucose → Insulin release

  • Between meals → Glycogen broken down → Glucagon increases blood glucose

3. Thirst Mechanisms

Body Fluid Compartments

  • Intracellular

  • Extracellular: interstitial fluid, plasma, cerebrospinal fluid

Types of Thirst

  1. Volumetric thirst — from reduced blood/plasma volume

  2. Osmometric thirst — from increased solute concentration in body fluids

4. Neural Control of Feeding

The brain integrates:

  • Hormones

  • Neurotransmitters

  • Behavioural drives

Neural circuits maintain homeostasis between energy intake and expenditure.

5. Hypothalamus: The Feeding Centre

The hypothalamus:

  • Links nervous and endocrine systems

  • Contains neuroendocrine cells

  • Monitors blood glucose and adiposity signals

Key Feeding Subregions

  1. Lateral hypothalamus (LH)

    • “Go eat!” centre

    • Stimulated → eating increases

    • Lesioned → reduced eating

  2. Ventromedial hypothalamus (VMH)

    • Satiety centre

    • Signals “stop eating”

  3. Arcuate nucleus (AN)

    • Detects hormones (leptin, ghrelin)

    • Regulates LH and VMH

Basic Feeding Circuit

  • Low glucose → LH activated → eat

  • High glucose → VMH activated → stop eating

6. Adiposity Regulation: Leptin

Leptin

  • Produced by adipose tissue

  • Level proportional to body fat

  • Acts as an “adipostat”

Effects

  • HIGH leptin → ↓ appetite, ↑ energy expenditure

  • LOW leptin → ↑ appetite

Arcuate Nucleus Peptides

Leptin State

Arcuate Peptides

Effect

HIGH leptin

CART, α-MSH

Suppress appetite

LOW leptin

NPY, AgRP

Stimulate appetite

MC4R

  • NPY/AgRP suppress melanocortin activity → increased feeding

  • MC4R mutations = most common inherited cause of obesity

7. Ghrelin — “Hunger Hormone”

  • Secreted by the stomach

  • Rises before meals, falls after eating

  • Enhances appetite and food-related thoughts (Schmid et al., 2005)

  • Responds to stomach filling, not blood nutrients

8. Role of Vagus Nerve

  • Carries satiety signals from gut → brain

  • Important in meal termination

9. Anti-Obesity Drugs

Sibutramine (Reductil)

  • SNRI → increases satiety, reduces metabolic suppression

  • Acts on the arcuate nucleus

  • Withdrawn due to cardiovascular risks

  • Similar action to amphetamines; dopamine/serotonin blockers also affect weight but with major side effects

PART 2 — Addiction

Learning Outcomes

  • Understand palatability and reward circuits

  • Understand dopamine’s role in motivation

  • Explain how drugs hijack reward pathways leading to addiction

1. Palatability & Reward

Palatable foods activate reward pathways:

  • Dopamine release reinforces eating

  • Ensures:

    • Learning about nutritious foods

    • Motivation to seek them

  • Blocking dopamine reduces consumption of tasty foods

2. Dopamine Basics

Dopamine is central to:

  • Reward

  • Motivation

  • Learning

  • Goal-directed behaviour

3. Liking vs Wanting

Concept

Meaning

Liking

Hedonic pleasure during consumption

Wanting

Motivation to obtain reward; driven by dopamine

Addiction

Transition from liking → wanting

Animals show wanting even when liking decreases.

4. Conditioning & Drugs

Self-administration

  • Animals voluntarily self-administer drugs

  • Drugs paired with pleasure → strengthen dopamine-dependent learning

Drug-taking becomes automatic

  • Behaviour becomes habitual

  • Occurs even when drug causes illness or harm

5. Reinforcement

Positive reinforcement

  • Drug → pleasurable effect → increased drug-taking

Negative reinforcement

  • Drug stops withdrawal symptoms → continued use

  • Addiction shifts from positive → negative reinforcement

6. Why Do Drugs Cause Addiction?

Drugs stimulate much larger dopamine surges than natural rewards.
This alters:

  • Learning systems

  • Motivation circuits

  • Habit formation

7. Alcohol

  • Increases endorphins → brief feeling of wellbeing

  • No single receptor; affects ion channels:

    • ↑ GABA

    • ↓ NMDA

  • Adaptation → tolerance

  • Hangover = mini-withdrawal

8. Key Definitions

Tolerance

Reduced response after repeated use.

Dependence

Need drug to avoid withdrawal; can occur without addiction.

Addiction

Compulsive use despite harm.

Relapse

Resuming use after abstinence.

9. Dopamine & Drugs of Abuse

Psychostimulants:

  • Act on dopamine transporters

  • Block or reverse them → ↑ dopamine in synapse

  • Also increase endogenous opioid release

  • Opioids disinhibit dopamine neurons → more dopamine

10. Reinforcement & Pharmacokinetics

  • Learning is strongest when effect occurs rapidly

  • Drink/inject drug → seconds

  • Pill → minutes/hours

  • Faster brain entry → higher addiction risk

Heroin vs Morphine

  • Heroin crosses BBB faster

  • Stronger reinforcement → more addictive

Nicotine vs MDMA

  • MDMA = more pleasurable

  • Nicotine = more addictive
    Why?
    → Route (inhalation = immediate)
    → Rapid dopamine spikes → strong habit formation

11. Addiction and the Prefrontal Cortex

PFC controls:

  • Impulse inhibition

  • Long-term planning

  • Decision making

Addiction:

  • Impairs PFC

  • Reduces ability to resist impulses

  • Leads to continued drug use despite consequences