Lecture 13: Addiction

Question 1

Basic Principles of Drug Addiction:

Drug Administration and Absorption

(4 ways)

Answer 1

1 of 4 ways; by oral ingestion, by injection, by inhalation or by absorption via the mucus membrane in either the nose, mouth, eye or rectum.

The route of administration influences the rate and degree to which the drug reaches its site of action in the body

Question 2

Basic Principles of Drug Addiction:

Drug Administration and Absorption

1. Oral injestion

Answer 2

Drug dissolves in fluids of stomach, carried to intestine, absorbed into bloodstream

Drugs that cannot be readily absorbed from the digestive tract or that are broken down into inactive metabolites before they can be absorbed must be ingested some other way

Some drugs, like alcohol, pass readily through stomach walls

Adv/ Easy and relatively safe
Disadv/ Unpredictability: Influenced by amount of food and type in stomach

Question 3

Basic Principles of Drug Addiction:

Drug Administration and Absorption

2. Injection

Answer 3

Strong, fast, predictable effects

• Subcutaneously (SC) into fatty tissue beneath skin
• Intramuscularly (IM) into large muscles
• Intravenously (IV) directly into veins

–> Bloodstream = directly to brain

Question 4

Basic Principles of Drug Addiction:

Drug Administration and Absorption

3. Inhalation

Answer 4

Absorbed through rich networks of capillaries in lungs e.g. anaesthetics (gas + air), marijuana, tobacco

Difficult to regulate dosage precisely

Question 5

Basic Principles of Drug Addiction:

Drug Administration and Absorption

4. Mucus membranes

Answer 5

Nose, mouth, rectum

Cocaine snorted through nasal membranes, damages them

Question 6

Drug Penetration of CNS

Answer 6

When a drug enters bloodstream, the blood brain barrier makes it difficult for dangerous blood-born chemicals to pass from blood vessels of CNS into its neurons

Question 7

Mechanisms of Drug Action:

Answer 7

Psychoactive drugs influence the nervous system - some act diffusely on neural membranes throughout CNS e.g. alcohol and some general anaesthetics

Others act in specific way: 
Bind to particular synaptic receptor to influence…
-	synthesis
-	transport
-	release
-	deactivation 
… of particular neurotransmitters 

OR by influencing the chain of chemical reactions elicited in post-synaptic neurons by activation of their receptors

Question 8

Drug Metabolism and Elimination:

Answer 8

Action of most drugs is terminated by enzymes synthesised by the liver - enzymes stimulate conversion of active drugs into non-active forms –> Drug Metabolism - Eliminates drugs ability to pass through lipid membranes of cells, can’t penetrate blood brain barrier

Small amounts of psychoactive drugs are passed from the body in urine, sweat, faeces, breath and mother’s milk

Question 9

Drug Tolerance:

Definition of drug tolerance

Answer 9

Drug tolerance is a state of decreased sensitivity to a drug that develops as a result of increased exposure

Question 10

Drug Tolerance:

Demonstrated in 2 ways

Answer 10

• Showing the same amount of drug has less effect than before
• Showing it takes more of the drug to produce the same effect

This phenomena can be represented by Dose Response Curves (graph of magnitude of effect of different drug doses) – tolerance is shown by a shift to the right

Question 11

Drug Tolerance:

3 important points about drug tolerance?

Answer 11

• Cross tolerance: One drug can produce tolerance to other drugs with similar mechanisms
• Drug tolerance often develops to some effects of a drug but not others

Drug Sensitisation: Increasing sensitivity to a drug

• Not a unitary phenomenon - no single mechanism underlies all drug tolerance, there are 2 main categories of tolerance

Question 12

Drug Tolerance:

Types of tolerance

(2 types)

Answer 12

Metabolic Tolerance: Drug tolerance that results from changes that reduce the amount of the drug getting to the sites of action

Functional Tolerance: Tolerance that results from changes that reduce reactivity of the sites of action to the drug

• Tolerance to psychoactive drugs is largely functional, can result from several types of adaptive neural change e.g. exposure to drug can reduce number of receptors for it, decrease efficiency for which it binds to receptors or diminish the impact of receptor binding on activity of the cell
• -> Neural changes can be caused by epigenetic mechanisms that affect gene expression

Question 13

Drug withdrawal Effects and Physical Dependence

Answer 13

Sudden elimination of a drug from the body can trigger adverse physiological reaction (withdrawal syndrome), evidence of physiological dependency

The effects of drug withdrawal are basically opposite to effect of drug e.g. effect of withdrawal from anticonvulsant drugs can trigger convulsions

Withdrawal effects are produced by same neural changes that produce tolerance –> Exposure produces compensatory changes in nervous system, offset drugs effect and produce tolerance, so when the drug is eliminated, compensatory neural changes, without drug to offset, them manifest themselves as withdrawals (opposite to initial effects of the drug)

Severity depends on drug, duration & degree of drug exposure and speed of elimination

Question 14

What is addiction?

Answer 14

Addict: Habitual drug user who continues to use drugs despite adverse effects on their health, social life, and despite their repeated efforts to stop

NOT the same as physical dependence, though this is often not motivating factor in addition

Food, gambling, sex additions may be based on similar mechanisms

Question 15

Role of Learning in Drug Tolerance:

Two types of learned drug tolerance

Answer 15

1. Contingent drug tolerance

2. Conditioned drug tolerance

Question 16

Role of Learning in Drug Tolerance:

1. Contingent drug tolerance

Answer 16

Demonstrations that tolerance develops only to drug effects that are actually experienced

Employs before and after design

e.g. painkiller and knee example

• take pk and get kicked in the knee
• knee doesn’t hurt because of pk
• repeat every day for a month
• tolerance to pk develops, stops working
• haven’t actually developed tolerance to pk just it’s effects on knee kicks

we know this because…

• different hypothetical scenario
• kick knee and give pk AFTER
• repeat for month
• knee hurts obviously
  THEN
• give painkiller BEFORE knee
• knee doesnt hurt, no tolerance to drug

Tolerance is contingent on experiencing the effects of it on knee bashing specifically

Question 17

Role of Learning in Drug Tolerance:

2. Conditioned drug tolerance

Answer 17

Demonstrations that tolerance effects are maximally expressed only when a drug is administered in the same situation it was previously administered –> Focuses on situations where drugs are taken

Addicts particularly susceptible to lethal effects of an overdose when drug administered in new context e.g. a new house, toilet cubicle etc

**Serious problem for health – we can have difficulty predicting direction of conditioned effects

Question 18

Role of Learning in Drug Tolerance:

2. Conditioned drug tolerance

Siegel’s Conditioned Compensatory Response Theory

Answer 18

Siegel’s Conditioned Compensatory Response Theory –

Sees each incidence of drug administration as a pavlovian conditioning trial, in which, various environmental stimuli regularly present when drug is administered act as predictors of drug administration.

Suggests conditioned environmental predictors come to elicit compensatory responses that are opposite to the action of the drug, to offset it’s effects. These compensatory responses become greater and greater with increasing incidence – producing situationally specific tolerance.

–> Ramsay and Wood argue unconditioned stimulus is disruption of neural functioning directly produced by drug, unconditional responses are various neutrally mediated compensatory reactions to unconditional stimulus

Types of stimuli:

• Exteroceptive stimuli - external stimuli like environment
• Interoceptive stimuli - internal stimuli like initial feelings produced by the drug ritual

Question 19

Five Commonly Abused Drugs:

List

Answer 19

1. Tobacco
2. Alcohol
3. Marijuana
4. Cocaine and other stimulants
5. Opiates: Heroin and Morphine

Question 20

Five Commonly Abused Drugs:

1. Tobacco

Overview

Answer 20

• Nicotine is the main psychoactive ingredient in cigarettes
• absorbed through lungs along with 4,000 other chemicals - ‘tar’.
• Non-smokers - nausea, vomiting, coughing, sweating, abdominal cramps, dizziness, flushing
• Smokers - relaxed, alert, less hungry
• withdrawal effects include depression, anxiety, restlessness, irritability, constipation, difficulty sleeping, difficulty concentrating
• 65% heritability for nicotine addiction (twin studies), 70% of people who experiment with smoking become addicted and only 20% of quitting attempts are successful after 2 years

Question 21

Five Commonly Abused Drugs:

1. Tobacco

Smokers Syndrome

Answer 21

Chest pain, laboured breathing, wheezing, coughing, heightened susceptibility to infections of respiratory tract

Smoking increases risk of cancer of larynx (voice box), mouth and heart, oesophagus, kidneys, bladder, pancreas, stomach

Relaxing effect of smoking reflects temporary reversal of stress caused by smoker’s addiction, stress is increased between cigarettes – smokers are more prone to panic attacks

Question 22

Five Commonly Abused Drugs:

1. Tobacco

Buerger’s Disease

Answer 22

Study - 15/100,000 people (mainly male smokers)

Characterised by blood vessels becoming constricted, especially those supplying legs

• Patient with condition continues to smoke, gangrene sets in, amputations occur, need to stop smoking for gangrene to clear up, people carry on even following 2-3rd amputation

Question 23

Five Commonly Abused Drugs:

1. Tobacco

Smoking doesn’t just affect smokers

Answer 23

Someone lives/works with smokers, more likely to develop heart disease and cancer

Nicotine is a teratogen (agent that can disturb normal development of foetus) - increases likelihood of miscarriage, stillbirth, early death of child
- Nicotine levels in blood of breastfed infants as great as those in blood of smoking others

Question 24

Five Commonly Abused Drugs:

2. Alcohol

Overview

Answer 24

• Alcohol molecules are small soluble, invade all parts of body
• Alcohol acts as a depressant, at moderate to high doses depresses neural firing
• Can also stimulate neural firing at low doses and facilitate social interaction
• 55% heritability to alcohol addiction
• Moderate doses, drinkers experience various degree of cognitive, perceptual, verbal and motor impairment + loss of control
• High doses, unconsciousness, blood levels reach 0.5% = risk from respiratory depression
• Facial red flush produced by dilation of blood vessels in skin, increases heat loss, causes decrease in body temp (hypothermia)
• Alcohol = diuretic, increases production of urine by kidneys

Question 25

Five Commonly Abused Drugs:

2. Alcohol

Tolerance

Answer 25

• Caused by heavy drinking
• Livers of heavy drinkers metabolise alcohol more quickly than non-drinkers, this contributes slightly to tolerance, most is functional
• Slight withdrawal produces nausea, vomiting, tremulousness (hangover)

Full Blown Withdrawal
- 5-6 hours after heavy drinking: Tremors, agitation, headache, nausea, vomiting, hallucinations sometimes
15-30 hours after: Convulsive activity
- 1-2 days after: Delirium Tremens (DT’s) – lasts 3-4 days: Disturbing hallucinations, bizarre delusions, agitation, confusion, hyperthermia (high body temperature) tachycardia (rapid heartbeat)

Question 26

Five Commonly Abused Drugs:

2. Alcohol

Korsakoff’s syndrome

Answer 26

Caused indirectly by alcohol

Neuropsychological disorder characterised by memory loss, sensory and motor dysfunction, severe dementia (in advanced stages) by inducing thiamine deficiency, increases susceptibility to stroke

Question 27

Five Commonly Abused Drugs:

2. Alcohol

Effects of alcohol on the brain and body

Answer 27

On the brain:
Alcohol reduces flow of calcium ions into neurons, interferes with function of second messengers inside neurons, disrupts GABAergic and glutaminergic transmission

On the body:

• Chronic alcohol consumption = cirrhosis of the liver
• Alcohol erodes muscles of heart, increasing risk of heart attack
• Irritates lining of digestive tract, increases risk of gastritis

Question 28

Five Commonly Abused Drugs:

2. Alcohol

Foetal Alcohol Syndrome

Answer 28

Alcohol readily penetrates placental membrane and acts as teratogen

FAS symptoms:

• brain damage
• mental retardation
• poor coordination
• poor muscle tone
• low birth weight
• retarded growth and/or physical deformity

No time during pregnancy where alcohol consumption is safe

Question 29

Five Commonly Abused Drugs:

2. Alcohol

Cure?

Answer 29

Disulfiram is drug that interferes with metabolism of alcohol, produces accumulation in bloodstream of acetaldehyde (one of alcohol’s breakdown products) high levels = dizziness, headache, vomiting, difficulty breathing, person medicated with Disulfiram can’t drink much alcohol without feeling ill, often people stop taking it the drug as a result

Question 30

Five Commonly Abused Drugs:

3. Marijuana

Overview

Answer 30

Cannabis Sativa – common hemp plant, people dry the leaves and flowers

• Smoked or ingested orally e.g. brownies - baked in oil rich substrate to promote absorption from gastrointestinal tract
• Psychoactive effects attributional to THC but marijuana contains over 80 cannabinoids – most found in sticky resin covering the leaves and flowers of the plant – can be extracted and dried to form a dark, cork-like material called hashish – further processes to form hash oil (really potent)

Marijuana was grown by loads of people for rope and was really popular for hundreds of years, thanks to the spread of misinformation on the effects of weed it was quickly classed as a Narcotic – legal term generally used to refer to opiates – in the 1900s.

Question 31

Five Commonly Abused Drugs:

3. Marijuana

Effects

Answer 31

Difficulty classifying effects, subtle, difficult to measure, greatly influenced by social situation
–> High dose: Impair psychological functioning, STM impaired, ability to carry out task involving multiple steps, slurred speech, sense of unreality, emotional intensification, paranoia, sensory distortion, motor impairment

Question 32

Five Commonly Abused Drugs:

3. Marijuana

Tolerance

Answer 32

Tolerance occurs through sustained use, uncommon to see obvious withdrawal symptoms

Long term effects less severe than alcohol and nicotine;

• respiratory problems
• tachycardia (high heart rate) so sometimes single large doses cause heart attacks in susceptive individuals, no direct evidence of brain damage

Good effects;

• can block seizures
• dilate bronchioles of asthmatics
• reduce severity of glaucoma
• reduces anxiety and some kinds of pain

2 possible behavioural effects due to marijuana, permanent memory loss (only found by 2 studies) and schizophrenia (users more likely to be diagnosed)

Question 33

Five Commonly Abused Drugs:

3. Marijuana

THC

Answer 33

Therapeutic effects
- Suppress nausea and vomiting

2 receptors for it in brain;

• CB1 – most prevalent G protein linked receptor in brain
• CB2 – found in brain stem and in the cells of the immune system – we have these receptors in our body for endogenous (naturally occuring) cannabinoid neurotransmitters – anandamide is an example

Question 34

Five Commonly Abused Drugs:

4. Cocaine and Other Stimulants

Answer 34

Stimulant: Drugs whose primary effect is to produce general increases in neural and behavioural activity

Functions as a catecholamine agonist, blocks reuptake of catecholamine’s (dopamine, norepinephrine, epinephrine) into presynaptic neurons

Snorting can damage nasal membrane

Question 35

Five Commonly Abused Drugs:

4. Cocaine and Other Stimulants

Effects/ Tolerance/ Withdrawal

Answer 35

Extremely high blood levels of cocaine reached during cocaine spree = sleeplessness, tremors, nausea, hyperthermia, psychotic behaviour
- Cocaine psychosis – syndrome of psychotic behaviour observed during cocaine spree

Tolerance develops to some effects (e.g. euphoria) repeated exposure increases users to its motor and convulsive effects

Withdrawals: Negative mood swing, insomnia, triggered by abrupt termination of cocaine spree, relatively mild

Question 36

Five Commonly Abused Drugs:

4. Cocaine and Other Stimulants

Other abused stimulants

Answer 36

Amphetamine (speed) and MDMA (ecstasy)

• Evidence suggests stimulants are neurotoxins
• MDMA can have toxic effects on both serotonergic and dopaminergic neurons
• Former users found to have deficiencies in these functions and abnormalities in areas of cortex and limbic system during tests of executive functioning, inhibitory control, decision making

Question 37

Five Commonly Abused Drugs:

5. Opiates: Heroin and Morphine

What are they?

Answer 37

Opium – sap that exudes from the seeds of the opium poppy- has several psychoactive ingredients

Morphine and codeine – weaker

Question 38

Five Commonly Abused Drugs:

5. Opiates: Heroin and Morphine

Effects

Answer 38

Opiates exert effects by binding to receptors whose normal function is to bind to endogenous opiates.

Endogenous opiate neurotransmitters that bind to such receptors are of 2 classes:

• Endorphins
• Enkephalins

Opiates – Jekyll and Hyde, one side analgesics (painkillers) and treat coughs and diarrhoea, other side extremely addictive

Morphine (most potent constituent of opium) – Addiction was common for those who could afford a doctor as morphine was used in loads of over the counter ‘remedies’ – used on soldiers in the war – morphine addiction became known as soldiers disease

Carminative: Drug that expels gas from the digestive tract thereby reducing stomach cramps and flatulence

Question 39

Five Commonly Abused Drugs:

5. Opiates: Heroin and Morphine

Harrison Narcotics Act 1914

Answer 39

banned sale or use of opium, morphine or cocaine other than medicinal prescription, act didn’t include the semisynthetic opiate heroin…

Question 40

Five Commonly Abused Drugs:

5. Opiates: Heroin and Morphine

Heroin - Effects/ Withdrawal

Answer 40

Effects:

• Rush follows intravenous injection – characterised by abdominal, orgasmic pleasure, drowsy euphoria
• Tolerance and physical dependence contribute to problem

Withdrawal:
Begins 6-12 hours after last dose; 
- Increased in restlessness
- watery eyes
- runny nose
- yawning
- sweating 
- then a fitful sleep, can last few hours
- followed by chills/ shivering
- nausea
- vomiting
- cramps
- diarrhoea
- dilated pupils
- tremors, muscle pain and spasms

Question 41

Five Commonly Abused Drugs:

5. Opiates: Heroin and Morphine

Heroin - direct health hazards

Answer 41

Although highly addictive, direct health hazards of exposure surprisingly minor
- Constipation
- Pupil constriction
- Menstrual irregularity
- Reduced libido (sex drive)
most medical risks of opiate addiction indirect, not attributional to drug itself

Serious risk is overdose, kills by suppressing breathing

Question 42

Five Commonly Abused Drugs:

5. Opiates: Heroin and Morphine

Heroin addiction treatment

Answer 42

Methadone, is an opiate, has same effect as heroin, produces less pleasure, strategy to block heroin withdrawal effects, marginally effective with addicts

Buprenorphine, high long lasting affinity for opiate receptors, blocking effect of other opiates on brain, does not produce powerful euphoria

Question 43

Biological Approaches to Theories of Addiction

Answer 43

• Early attempts to explain addition was attributed to by physical dependence
• This traps addicts in vicious circle of drug taking and withdrawal symptoms
• Attempted to gradually withdraw drugs from addicts in hospital environment to break cycle

Detoxified Addicts: Addicts who have no drugs in their bodies and are no longer experiencing withdrawals

Failure of detoxification as a treatment not surprising…

• Some additive substances e.g. cocaine does not produce severe withdrawal symptoms
• Patterns of drug taking by addicts involves an alternating cycle of binging and detoxification
• -> New approach dominated in 70’s and 80’s (Positive incentive theory)

Question 44

Positive Incentive Theories of Addiction:

Overview

Answer 44

New approach based idea that most addicts take drugs not to escape or to avoid unpleasant consequences of withdrawal but to obtain the positive effects
–> Craved positive incentive

These types of theories need to offer explanations for 2 puzzling aspects of drug addiction:

1. Big difference between hedonic value of the drug and the positive incentive value of the drug (hedonic value = amount of pleasure actually produced, addicts report huge discrepancy)
2. Must be able to explain how a drug user transforms into an addict, many people periodically use addictive drugs without becoming addicted

Question 45

Positive Incentive Theories of Addiction:

Incentive-Sensitisation Theory

Answer 45

Incentive-Sensitisation Theory:

• -> Meets these 2 requirements
• Positive-incentive value of the drug increases with drug use
• Use of drug sensitises drugs positive incentive value rendering such individuals highly motivated to seek and consume drug
• In addicts, positive-incentive value of the drug is often out of proportion with the pleasure experienced from it (they want to take it more than they like taking it)

Question 46

Relapse and Causes

Answer 46

Propensity to relapse – return to drug taking habits even after a long period of voluntary abstinence is hallmark of addiction

3 fundamentally different causes identified:

1. Stress
2. Drug priming
   - -> single exposure to formally used drug, person could sample their formally used addiction behaviour just once and immediately are plunged back into full addiction
3. Exposure to environmental cues
   - -> cues that predict drug exposure come to elicit conditioned compensatory responses through conditioning and because conditioned compensatory responses are often opposite to original drug effect they produce tolerance – explains why Vietnam soldiers were able to shed their addictions when returning home

Question 47

Intracranial Self-Stimulation and the Pleasure Centres of the Brain:

Answer 47

Intracranial self-stimulation (ICSS) – rats, humans and other species will administer brief bursts of weak electrical stimulation to specific sites in their own brains

Brain sites capable of mediating phenomenon called pleasure centres

Olds and Milner (1954) – specific brain sites that mediate self-stimulation are those that normally mediate the pleasurable effects of natural rewards e.g. food, water and sex.

But pressing the lever for food and water is very different from pressing a lever for ICS

Question 48

Intracranial Self-Stimulation and the Pleasure Centres of the Brain:

pressing the lever for food and water is very different from pressing a lever for ICS

Answer 48

Puzzling observations contributed to this view…

1. Despite extremely high response rates, many rats stopped pressing self-stimulation lever almost immediately when currently delivery mechanism was shut off – weird, would you stop pressing a button that’d been giving you money the first few times it stopped delivering money? Probably not
2. Experienced self-stimulators often didn’t recommence lever pressing when they were returned to the apparatus after briefly being removed from it, rats had to be primed to get them going again

Research indicates circuits mediating ICSS are natural reward circuits

• Brain stimulation through electrodes that mediate self-stimulation often elicits a natural motivated behaviour (e.g. drinking)
• Producing increases in natural motivation (e.g. food or water deprivation) often increases self-stimulation

Question 49

Mesotelencephalic Dopamine System and ICSS:

Answer 49

The mesotelencephalic dopamine system plays an important role in intercranial self-stimulation.

System of dopaminergic neurons that projects from the mensephalon (the mid-brain) into various regions of the telencephalon

Neurons that compose of the mesotelencephalic dopamine system have their cell bodies in two midbrain nuclei:

1. Substantia nigra
2. Ventral tegmental area
   - These cell axons project to variety of telencephalic sites

Most axons of dopaminergic neurons have their cell bodies in (1) substantia nigra project to the dorsal striatum –> this is called the nigrostriatal pathway –> degeneration in this pathway associated with Parkinson’s

Most axons of dopaminergic neurons have their cell bodies in the (2) ventral tegmental area project to various cortical and limbic sites –> Mesocorticolimbic pathway

Research supports views that Mesocorticolimbic pathway of the Mesotelencephalic dopamine system plays an important role in mediating ICSS:

1. Many of the brain sites at which self-stimulation occurs are part of the Mesotelencephalic dopamine system, or project directly to the system
2. ICSS often associated with an increase in dopamine release in the Mesocorticolimbic pathway
3. Dopamine agonists tend to increase ICSS, and dopamine antagonists tend to decrease self-stimulation
4. Lesions of Mesocorticolimbic pathway tend to disrupt ICSS

Question 50

Early Studies of Brain Mechanisms of Addiction: Dopamine

Answer 50

Experience of pleasure linked is to mesocorticolimbic pathway

Specific brain mechanisms could not have evolved for the purpose of mediating addiction –> drug addiction is not adaptive, so studying areas implicated in experience of pleasure should help solve how the pleasure experienced when taking drugs occurs

Key to understanding neural mechanisms of addiction lies in understanding natural motivation and how they are co-opted and warped by addictive drugs

Question 51

Two Key methods for measuring drug-produced reinforcement in laboratory animals:

Answer 51

1. Drug self-administration paradigm:
   - Animals press lever to inject drugs into themselves by implanted cannulas (thin tubes)
   - Readily learn to self-administer drugs that humans find addictive
   - Once learnt, drug taking in some respects mimics that of human drug taking
2. Conditioned place-preference paradigm:
   - Repeatedly receive drug in one compartment of a two-compartment box
   - Drug free rat then placed in box, proportion of time spends in drug compartment measured
   Advantage – subjects tested whilst drug free, no confounding effect of the drug

Question 52

Early evidence for Dopamine in Drug Addiction:

Answer 52

Research of dopamine in inter-cranial self-stimulation began to implicate dopamine in the rewarding effects for natural reinforcers and addictive drugs

Question 53

Nucleus Accumbens and Drug Addiction:

Answer 53

• Explored sites in Mesocorticolimbic dopamine pathway by conducting experiments on lab animals
• Events occurring in Nucleus Accumbens and dopaminergic input to the Mesocorticolimbic dopamine pathway from the ventral tegmental areas appeared to be most clearly related to experiencing pleasure and reward

Question 54

Imaging human brains – Involvement of Dopamine in Addiction:

Answer 54

Volkow et al (1997)

• Administered various doses of radioactively labelled cocaine to addicts and asked to rate the resulting high
• Used PET to measure the degree to which the labelled cocaine bound to dopamine transporters (molecules in the presynaptic membrane of dopaminergic neurons that attract dopamine molecules in the synaptic cleft and deposit them back into the neuron)
• Cocaine has its agonistic effects on dopamine by blocking the reuptake, intensity of highs correlated with degree to which cocaine bound to the dopamine transporters – thus how much extracellular levels of dopamine are increased – no high is experienced unless cocaine bound to 50% of the dopamine transporters
• Brain imaging studies also found the Nucleus Accumbens is important in mediating the rewarding effects of addictive behaviour – euphoria is experienced when dopamine levels in the nucleus accumbens as a result of drug action – the area becomes hyperactive when addicts are exposed to the drug or stimuli associated with the drug despite the fact that usually, dopamine action is reduced in addicts

Question 55

Nucleus Accumbens - mediates the rewarding effects of addictive behaviour – euphoria is experienced when dopamine levels in the nucleus accumbens as a result of drug action - area becomes hyperactive when addicts are exposed to the drug or stimuli associated with the drug despite the fact that usually, dopamine action is reduced in addicts

Dopamine Release in Nucleus Accumbens – Reward or Expectation of Reward?

Answer 55

Disagreement in precise role of dopamine release in reward about whether dopamine release in the nucleus Accumbens is related to the experience of reward or expectation of reward

Evidence for Experience of Reward:
Ventral tegmental neurons – release dopamine into nucleus accumbens, fire in response to a stimulus at a rate proportional to its reward

HOWEVER, …
Several studies suggested neutral stimuli that signal the impending delivery of reward can themselves trigger dopamine release in nucleus accumbens, suggests dopamine release in nucleus accumbens is associated with expectation of reward rather than experience

Resolving Discrepancies:

1. Stimuli that signal rewards can develop rewarding properties of their own- thus if the nucleus accumbens mediates the experience of reward, it should respond to its predictive cues
2. Tobbler, Forillo and Schultz, (2005) - Dopaminergic neurons with their cell bodies in the ventral tegmental area fire at a rate related to the value of reward, so when an expected reward was delivered the firing rate stayed the same, less than expected = firing rate decreased, more than expected = firing rate increased  dopamine levels in the nucleus accumbens DO reflect reward value but NOT in a straightforward way…

Question 56

Current Approaches to Brain Mechanisms of Addiction:

Quick history recap:

Answer 56

Quick history recap:

One line of original theory focused on physical dependence – not sufficient – could just hold people until detoxed but that doesn’t solve problems/ some addictive drugs don’t cause withdrawal

–> this evolved into positive incentive theories of addiction and a focus on dopamine and pleasure centres in the brain (mesocorticolimbic pathway and mechanisms of reward)

–> A second line developed from the idea of conditioned responses in drug tolerance (conditioned compensatory responses and drug tolerance) – major factors in drug craving and relapse

Question 57

Current Approaches to Brain Mechanisms of Addiction:

Brain Mechanism of Addiction – Recent Developments

Answer 57

> Addiction is psychologically complex; drug addicts differ psychologically from healthy controls in a variety of ways

• Poor decisions
• Excessive risk taking
• Deficits in self control
• -> Treatments must take these differences into account

> Addiction involves many parts of the brain

• Mesocorticolimbic pathway plays an important role in drugs addiction
• Prefrontal cortex is great interest because addicts display patterns of behaviour typical of those who have sustained damage to that area
• Prefrontal cortex also receives input from the ventral tegmental area
• Roles of amygdala and the hippocampus because of their interactions with the prefrontal cortex and the Mesocorticolimbic system

> Addiction involves many neurotransmitters
- Role of glutamate in addiction suggests several neurotransmitters are involved

> Addiction not limited to drugs

• Several other behaviours exhibit defining features of drug addiction – inability to refrain from a behaviour despite the adverse effects
• Examples include: gambling, kleptomania (shoplifting), compulsive shopping, compulsive sexual behaviour

Question 58

Current Approaches to Brain Mechanisms of Addiction:

Brain structures that mediate addiction – Current View

Answer 58

Three stages of addiction:

1. Initial drug taking
2. Change to craving and compulsive drug taking
3. Relapse
4. Initial Drug Taking:
   Initial taking of drugs thought to be mediated in the same way as any pleasurable activity – with the Mesocorticolimbic pathway – in particular nucleus accumbens – playing an important role
   a) Prefrontal lobes – Role in decision to take the drug
   b) Hippocampus – Provide information about previous experiences
   c) Amygdala – Coordinate positive or negative emotional reactions to drug taking
5. Change to craving and compulsive drug taking:
   Repeated consumption brings major changes in motivation of the developing addict
   - Develops into a habit then a compulsion
   Change in how the striatum reacts to a drug and its associated cues
   - As addiction develops, striatal control of addiction spreads from the nucleus accumbens to the dorsal striatum (area that plays a role in habit formation and retention)
   - Role of prefrontal cortex in controlling behaviour declines (mediates decision making)
   - Stress circuits in the hypothalamus begin to interact with the dorsal striatum
6. Development of addiction is a pathological neuroplastic response that some people show with repeated drug taking

Relapse:
Factors known to trigger relapse:
1. Priming doses of the drug
2. Drug associated cues
3. Stress
Each cause of relapse mediated by the interaction of different brain structures with the striatum
•Prefrontal cortex- mediates priming-induced relapse
•Amygdala- mediates conditional cue-induced relapse
•Hypothalamus- mediates stress induced relapse