Reward and Addiction

I got a few books on drugs, reward and addiction, but best book in my opinion is

Drugs & Behaviour: An Introduction to Behavioral Pharmacology by William McKim (click image).

 

DEFINITIONS

Stimulants: drugs producing increases in neural & behavioural activity

 

COCAINE

effects: well-being, confident, energetic, outgoing, fidgety, less appetite & less sleep

cocaine spree: high intake for couple days; tolerance >> larger doses >> sleeplessness, tremors, nausea, cocaine psychosis; risk of loss of consciousness, seizures, heart attack, stroke

cocaine psychosis: psychotic behaviour similar to paranoid schizophrenia

– repeated use makes people more responsive to motor & convulsion effects

– withdrawal effects relatively mild: negative mood swing & sleeplessness

– blocks DA reuptake transporters

 

AMPHETAMINES (speed); also meth and crystal meth + MDMA (ecstacy)

– effects similar to cocaine

– increases levels of DA

 

OPIATES: HEROIN & MORPHINE

Opium: key psychoactive ingredients are morphine and codeine

Heroin: synthesized by adding 2 acetyl groups to morphine (penetrates blood-brain barrier)

– opiates bind to opiate receptors

Heroin rush: intense abdominal orgasmic pleasure, then drowsy euphoria

– high use >> tolerance >> physical dependence

– withdrawal symptoms 6-12 hours: tremor, sweating, vomit, gooseflesh, muscle spasms

 


 

ROLE OF DOPAMINE IN REWARD & ADDICTION

 

INTRACRANIAL SELF-STIMULATION (ICSS) – ELECTRICAL

Olds & Milner (1954)

– rats/ people give themselves weak electrical stimulation to pleasure centres in brain via lever presses

– these pleasure centres also give pleasure when having food, water, sex: natural reward circuits (ensure we repeat)

– studied self-stimulation in various brain sites to map relevant neural circuits

 

MESOTELENCEPHALIC DOPAMINE SYSTEM

– the mesocorticolimbic pathway in the mesotelencephalic DA system is key in ICSS:

1) ICSS happens at brain sites that are part of this DA system

2) ICSS associated with DA increase in this pathway

3) DA agonists increase ICSS; DA antagonists decrease it

4) Lesions in pathway disrupt ICSS

 

drug reward pathways nucleus accumbens ventral tegmental area

 

NUCLEUS ACCUMBENS & DRUG ADDICTION/ STIMULATION – DRUG

– dopaminergic input from ventral tegmental area to n.acc were clearly related to reward & pleasure (e.g. Deadwyler et al 2002):

1) Animals self-administered additive drugs directly into n.accumbens

2) High rates lever pressing for drugs increasing DA activity

3) Injections of drugs in n.acc >> conditioned place preference

4) Lesions to n.acc blocked self-admin & place preference

5) Self-admin of drugs and natural reinforcers associated with higher DA in n.acc

 

Volkow et al (2004) – PET (positron emission tomography) scan shows ‘highs’ related to DA reuptake transporter binding

– seeing drug paraphernalia causes n.acc to become hyperactive

 

Drevets et al (2001) – scan shows amphetamine induced DA increase in n.acc >> greater euphoria

 

ACUTE EFFECTS & DA

– Volkow et al (1997) – degree of DA binding related to self-reported ‘high’

– more DA receptors in brain of overdosed compared to other addicts

 

Weiss et al (2000) – expectation

– expectation of reward releases DA in n.acc

– experience of reward & its value related to firing rate of ventral tegmental neurons

 

Tobler et al (2005) – difference in actual vs. expected reward determined firing

 

Schultz (1997) – article “Dopamine neurons and their role in reward mechanisms” (review of studies)

– research shows that DA neurons activate for primary rewards and reward predicting stimuli

– these neurons activate with differences to the expected event (unpredictability)

– this is when learning happens best

– studies show addictive drugs activate DA mechanisms in n.acc & frontal cortex

 

EVIDENCE OF INVOLVEMENT OF DA IN DRUG ADDICTION

– DA agonists block drug self-admin & place preference so DA signals reward/ pleasure

– drug’s rewarding effects related to its ability to release DA esp. in n.acc

 

WHAT IS DOPAMINE DOING/ PURPOSE IN TERMS OF REWARD?

– lecture said “we don’t know”

  1. does it make us like stuff? DA is pleasure NT
  2. does it make us want stuff? DA creates associations
  3. does it make us learn stuff? DA makes us remember to do something

no3. has link with Schultz’s & Weiss’s work above

 

McKim (2007) explains it as follows:

  • activation of the mesolimbic dopamine system causes behaviour to be repeated
  • it is not a feel good system but a ‘do-it-again’ or ‘wanting’ system

Involves:

  1. mesolimbic DA system – the reinforcement system
  2. the basal ganglia – the motor system
  3. hippocampus & amygdala – the learning & memory system

It has 2 roles in motivating behaviour:

  1. general activation (e.g. when hungry, move)
  2. direct behaviour to a goal via incentive salience, based on previous outcomes

 


 

BIOPSYCHOLOGICAL APPROACHES TO THEORIES OF ADDICTION

 

Addiction: a drug producing withdrawal effects after stopping

 

PHYSICAL DEPENDENCE/ NEG REINFORCEMENT THEORIES

– feeling of not being able to function normally without drug: reinforcing

– withdrawal symptoms drive a dependent user to crave when they attempt to stop

– so treatment in hospital gradually reducing dosage

BUT didn’t work:

1) some addictive drugs (e.g. cocaine & amphet) don’t have severe withdrawal

2) binges and detox is a normal pattern (free weekends, no money, jail)

3) highly addictive drugs e.g. cocaine don’t show withdrawal effects/physical dependence

4) some drugs produce physical dependence but aren’t abused

5) doesn’t explain relapse after long abstinence when not in withdrawal

6) minimises positive effects of drug: this is why they continue (chasing the high)

7) don’t explain why people become addicts in the first place: to do with reinforcement

8) withdrawal symptoms don’t predict relapse so little predictive validity

BUT

Baker et al (2006)

  • withdrawal plays an important part in drug motivation and relapse
  • studies need to consider chemical and drug injection ritual etc withdrawal
  • withdrawal symptoms are highly predictive of relapse

 

POSITIVE-INCENTIVE THEORIES

– drugs are positive reinforcers, following the same rules as other reinforcers

– ICSS studies show drugs are positive reinforcers

– drugs activate the mesolimbic DA system by stimulating the n.acc

VS natural reinforcers, the difference with drugs is:

  1. they don’t have a satiation mechanism (as with water) – there’s no limit to their reinforcing ability
  2. drug’s effect is stronger and more immediate >> stronger reinforcement

BUT: paradox – why do animals/ humans persist when consequences can be deadly?

THO: same as other reinforcers e.g. food; could also that be painful effects are delayed

 

INCENTIVE-SENSITIZATION THEORY

Berridge & Robinson (2009)

– drug craving is manifestation of incentive salience

– drugs are a positive reinforcer: they activate mesolimbic DA system >> want

– salience gets stronger with more drug use because of sensitization of mesolimbic DA sys

– the drug and associated stimuli motivate approach, wanting and craving

– it is not liking or pleasure: this is another brain system

SUPPORT:

  1. explains addiction: first not a strong reinforcer then gets stronger
  2. explains why paraphernalia & locations etc cause craving & relapse
  3. brain imaging shows more attention/ focus on drug related stimuli by addicts and former addicts (e.g. Franken et al 2003)

(Fred Toates said theory is most/ heavily cited: very influential)

 

1) Addiction theories need to explain difference bet. expectation and experience of drug

Positive-incentive value: anticipated pleasure

Hedonic value: actual pleasure experienced

2) Many people get hedonic pleasure without getting addicted

I-S theory: more use >> increased anticipation; it’s less about the pleasure

 

KOOB & LeMOAL (2001) – HEDONIC DYSREGULATION – modern dependence theory

Homeostasis: physiological processes have optimal set point that’s maintained

Allostasis: set point changes because of changes in the environment

  1. person starts at a certain normal mood set point
  2. drugs cause pleasure by activating n.acc and the “extended amygdala”
  3. mood increases above normal then decreases below normal (dysphoria)
  4. mood then returns to its set point, but this set point gets lower with repeated use
  5. user must take more drug to bring mood back to previous normal level

– lowered set point reduces reinforcing effect of drug & other reinforcers

– but drug is still the most powerful reinforcer >> accelerating addiction

– K&M observed changes in extended amygdala and hormone responses of brain

– agree with Robinson & Berridge’s sensitization but early addiction only: overcome by Hedonic dysregulation (lowered mood point)

 

CURRENT QUESTIONS THAT THEORIES SHOULD ACCOUNT FOR

Volkow (2006) – drug addicts are poor decision makers & risk takers. Indiv psychological differences

Cardinal (2004) – addiction is disturbance in decision making. Why do something harmful?

Koob (2006) – addiction must be more than DA: NA, GABA, endogenous opioids

 

CURRENT VIEW – BRAIN STRUCTURES INVOLVED IN ADDICTION

  1. INITIAL DRUG TAKING:

N.acc together with –

Grace et al (2007): PF lobes decision; hippocampus previous experiences; amygdala positive/ negative emotions

 

  1. CHANGE TO CRAVING AND COMPULSIVE DRUG TAKING

Koob (2005) – a pathological neuroplastic response (e.g. n.acc to dorsal striatum connection to habit)

 

  1. RELAPSE

Research: PFC – primming; amygdala – cue relapse; hypothalamus – stress response

 


 

ARTICLE: Volkow & Goldstein (2002) – “drug addiction & its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex”

  • was thought addiction involved reward processes connected to limbic circuits
  • but Volkow argues scans show PFC is additionally involved
  • most studies focused on DA in addiction because it’s important for drug reinforcing effects
  • BUT DA alone doesn’t explain why addicts report smaller highs with high DA
  • means that DA role works with functional & structural changes in DA related circuits, including frontal cortex

Addiction is cortically regulated cognitive & emotional process that:

  1. Causes overvaluing of drug reinforcers/ stimulus
  2. Cause deficits in inhibitory control/ self-will for drug responses in frontal cortex

These changes Volkow calls I-RISA: impaired response inhibition & salience attribution

Reinforcement >> Craving >> Bingeing >> Withdrawal >> Reinforcement (repeat in a cycle)