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Flashcards in Pleasure And Addiction Deck (37):
1

What gives pleasure?

Brain reward regions are activated only where an attractive person is gazing at you (Kampe et al. 2001)

2

Olds and Milner (1954) - Brain pleasure centre

Rats work to obtain stimulation from electrode implants
100 times a minute for hours
Learn complex tasks to obtain it
stimulation chosen at cost of starvation (Routtenberg, 1978

3

Why is the Dopamine pathway important?

Self stimulation is rewarding to rats if it stimulates dopamine release (Crow, 1972)

Phillips et al. (1989) an increase of dopamine release in NUCLEUS ACCUMBENS during brain self stimulation

The increase is proportional to rate and intensity of stimulation

4

Nucleus Accumbens, nicotine and dopamine

dopamine release in nucleus Accumbens increased by nicotine

5

Activation of mesolimbic dopamine system

Common to all rewards:
Food, sex, drugs of abuse

Self stimulation

Even playing a video game (Koepp et al., 1998)

And seeing an attractive face gazing at you

6

Dopamine blockers antagonists reduce rewards - stellar et al 1983

Injected dopamine blockers (antagonist) into nucleus accumbens stops rats working for electrical stimulation

Dopamine antagonist reducing rewards and motivation of self stimulation

7

Theories of dopamines role
1. Paths hedonism hypothesis (Wise, 1982)

Brain mediates dopamine and therefore pleasure
The dopamine system is where "sensory inputs are translated in to the hedonic messages we experience as pleasure or euphoria"

8

Hedonic hypothesis and addiction

Pleasure and pain motivates drug use
Try it like it
Without it experience pain of withdrawal

However, does not consider relapse and craving

9

Theories of dopamines role
2. Opponent process model (Solomon and Corbit, 1974)

A stimulus which causes positive affects (pleasure) automatically sets in motion an opposite affective response (displeasure)

Repeated use (neuroadaption): lowering of hedonic set points
Chronic users experience dysphasia in Absense of drugs

10

Is DA really about pleasure? Does it have a different function?

Measuring of dopamine release during rewarding behaviour
Plays et al (1990) - male rat respirate from a female rat in a second chamber. Dopamine release was higher at anticipation of sex rather than after sex

Role of DA pathway?
DA energises behaviour - like a shot of amphetamine
need most energy not when you have goal, but when you have the possibility of achieving it

11

Theories of dopamine
3. Incentive salience hypothesis - Berridge and Robinson (1998)

- wanting and liking are different

- DA system controls wanting but not liking

- this system can transform a stimulus into something important and desirable

- drug abuse causes long term changes to this desire syste,. becomes hyper sensitised - causing long lasting craving

- Causes a person to be attentive and motivation towards rewarding stimuli

12

Theories of dopamine
3. Incentive salience hypothesis - Berridge and Robinson (1998)

Drugs and other stimuli can still give pleasure but the dopamine system is not involved in these feelings

It does not 'mediate the hedonic impact of a stimulus' (Berridge and Robinson, 1998)

It stimulates WANTING (craving)

13

Berridge and Robinson (1996, 1998)

Destroy (6-OHDA) or block dopamine pathways

rats won't work for sucrose but still like it

Perhaps it isn't a reward pathway

Supports incentive salience theory

B&R : addiction is caused by craving and DA system is a wanting/craving system

Addicts DA system sensitives : Long lasting sensitivity/craving for rewarding drug

14

More evidence for DA activation in anticipation - Chilsress et al 1996

Video of pretend drug use shown to addicts

Addicts craving - dopamine system activated

Sex video - same areas of the brain activated

Before a meal (Martel and Fantino, 1996)

Before drug (Gratton and Wise, 1994)

Before sex

Difficult to explain doe hedonic hypothesis

15

Dopamine is not just pleasure

Mazindol: potent DA against does not produce cocaine like euphoria

L-Dopa: increases DA but not euphoria

Increasing DA transmission is not sufficient euphoria

16

Problems?

DA antagonists can increase drug taking (smoking - Rose and Corrigal, 1997)

DA agonists can decrease ethanol drinking in alcohol preferring rats (McBride and Li, 1998)

Dopamine has multiple roles in reward and liking

17

Discriminating between theories

Need to measure liking NOT wanting
Most measures don't (eg lever pressing)
Do they like it or do they want it

18

Use 'affective' reactions
- Human facial reactions

Rats: taste reactivity test

Hedonic
- Lateral and rhythmic tongue protrusions and paw licks

Aversive
- Chin rubs, face washing, locomotion

Neutral
- Rhythmic mouth movements

19

What is pleasure?

Berridge (2003)
- Opiate system may mediate pleasure (liking) and it is part of the mesolimbic dopamine pathway(nucleus accumbens shell)

- Craving (wanting) system is also part of mesolimbic dopamine pathway and independent of liking

20

What are the three theories of dependence?

Mesolimbic DA system
- Activation common to cocaine, heroin, nicotine and amphetamines
1. Hedonia, pleasure system (Reward and withdrawal model)
2. Incentive, motivation, craving system (Incentive Salience model)
3. Rebound effects (opponent process model)

21

Weaknesses and pulses of the models

Opponent process and incentive salience
- The two models don't really explain reward effects - why people start using drugs

- Incentive salience explains craving
- Opponent process explains dysphasia

22

social context and occasional use

Approximately 80% of US Army abused opiates in Vietnam

Most never used it when returning home (14%) (Robins et al., 1975)

In US 90% relapse rage in heroin addicts (Brecher, 1972)

Rats in isolation take 8x more morphine solution than rats in social environment (Alexander et al 1985)

23

Withdrawal

Adverse reactions to Absense of drug

Symptoms: often opposite effects of drug

Cocaine has no specific withdrawal syndrome but most addictive drug

depression, anxiety, agitation, anhedonia

24

Intensity of withdrawal correlates with intensity and duration of drug effects

Immediacy if reward and addictive ess
- Most addictive - immediate effects (cocaine)

- Heroin preferred to Morphine: has immediate effects

- Rush effect

25

Tolerance

Decreased sensitivity to drug and need leader amounts for same effects

1. Central (receptor) effects
- Desensitisation of receptors

2. Peripheral (liver) body changes
- Better at breaking down drug

26

Repercussion of tolerance

Larger doses and more frequently: toxic effect of drug develops

Tolerance differed for drug effects
- More tolerance for pleasure effects than negative effects for Amon and cocaine

Also cross tolerance: alcohol and barbiturates

More tolerance for sedative than anxiolytics effects for BZs

27

Reverse tolerance (sensitisation)

In some cocaine users they become more sensitive to effects of drug

Intoxication, psychosis etc at low doses

Repeated stimulation of DA pathway changes its functioning

Can last up to a year

Interacts with stress, cross sensitisation

28

Context specific tolerance

Pavlovian conditioning of tolerance to drug related stimuli

Heroin addict: drug related stimuli initiate tolerance response

29

DA Priming

An increase in :- release can increase craving and relapse

Stress increases DA release and increases drug craving and drug seeking

Smokers increase intake during exams (Warburton, 1987)

Shazam and Stewart (1995) - Heroin abstinent rats quickly began self administering heroin again when stressed

30

Craving often causes relapse (after withdrawal) B&R, 1998

Heroin addicts work for injections with minute morphing doses which give no reward

Don't work for placebo injections
Morphine imperceptibility increasing craving by boosting DA craving pathway

31

Implications for overcoming drug addiction

Change social context
Practice overcoming craving
Remove any drug related stimuli
stop using other drugs
Reduce stress
Avoid withdrawal
Increase natural and alternative rewards

32

Drug treatments for drug abuse

Replacement therapy
(B&R may predict that this is not a good idea)

Opiates
Eg methadone
LAAM

smoking
Patch, gum, nasal spray

33

Blocking effects of drug

Naltrexone (opioid antagonist)
- Blocks receptors for 24-48 hours
- Reverses overdose

Rapid Detox
- Withdrawal and detox while anaesthetised (Legarda and Gossop, 1994)
- Vomiting, diarrhoea

Long term use
- Removes effects of opioids
- Problem: craving still there
- Naltrexone - 73% dropout
- Methadone 13% dropout

34

Vaccines

Immune system produces antibodies to attach to drug so molecules too large to reach brain reward areas

eg nicotine (Pental et al, 2000; Vocci and Chiang, 2001)

BUT may prevent nicotine therapy alleviating nicotine withdrawal (Malin et al 2001)

35

Zyban (Bulropion, Wellbutrin)

Antidepressant, anti obesity, anti smoking
Amphetamine like, mild DA agonist. Also increases NA release
Alleviates craving, good increase in quit rates

How does it work?
A small boost in DA activity by Zyban may function to replace that lost by smoking
Wouldnt be predicted from B&R theory
Natural rewards might do the same

36

Summary

Addictive drugs act on DA system in subtly different ways

Pharmacological treatments will have to be different for different drugs

Perhaps treatments should be determined by what works rather than theory of addition or political view point

37

What is reward? Why are they important?

Subjective pleasure
Hedonic impact of a stimulus
Fundamental for motivation and goal seeking behaviour
Basis for instinctive drives: hunger, thirst, sex
Substrate of more complex States: desire, motivation, ambition, goals