Pleasure And Addiction Flashcards
What gives pleasure?
Brain reward regions are activated only where an attractive person is gazing at you (Kampe et al. 2001)
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
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
Nucleus Accumbens, nicotine and dopamine
dopamine release in nucleus Accumbens increased by nicotine
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
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
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”
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
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
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
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
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)
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
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
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
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
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
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
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
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)
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
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)
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
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
Tolerance
Decreased sensitivity to drug and need leader amounts for same effects
- Central (receptor) effects
- Desensitisation of receptors - Peripheral (liver) body changes
- Better at breaking down drug
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
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
Context specific tolerance
Pavlovian conditioning of tolerance to drug related stimuli
Heroin addict: drug related stimuli initiate tolerance response
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
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
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
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
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
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)
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
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
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
