Lecture 6: Psychiatric Disorders, Drug Action and Addiction

Question 1

What are drugs?

Answer 1

• Substances similar to substances already present in our nervous systems.
• Particularly similar to those affecting at the synapse.
• Substances present in the natural world - mainly from plants.
• Plants produce the chemicals to attract/repel insects or for own process.
• Nervous systems of animals are very similar so also act on humans.

Question 2

How do drugs work?

Answer 2

• Facilitate or inhibit transmission of nerve impulse at the synapse.
• Drug has high affinity for a receptor if it binds to it (may not activate the receptor)
• Drug has high efficacy if activates the receptor.
• Most drugs stimulate the release of dopamine.
• Particularly in the nucleus accumbens (reward centre).
• Area rich in dopamine receptors.
• Drug -> sustained bursts of dopamine (usually inhibitory) -> inhibits GABA (gamma - aminobutyric acid, important inhibitory transmitter) -> increases in nucleus accumbens.

Question 3

What are the effects of Agonistic drugs?

Answer 3

• Increases synthesis of NT.
• Increases the number of the NT by destroying degrading enzymes.
• Increases the release of NT.
• Binds to presynaptic receptors and block inhibitory effect.
• Binds to postsynaptic receptors and activates or increases the NT effect.
• Blocks the deactivation of NT by blocking their degradation or reuptake.

Question 4

What are the effects of Antagonistic drugs?

Answer 4

• Block synthesis of NT.
• Causes the NT to leak and to be destroyed.
• Blocks the release of NT.
• Activates the receptors and inhibits NT release.
• Binds to receptors and blocks the effects of NT.

Question 5

How do stimulant drugs work?

Answer 5

*Amphetamine (speed): Stimulates dopamine synapses by increasing the release of dopamine from presynaptic terminal.
*Cocaine: Blocks the reuptake of dopamine, thus prolonging effects.
= Dopamine agonists.
*Accumulation of dopamine in the synaptic cleft.
*More dopamine = widespread reduction in activity in most of the brain (except nucleus accumbens).

Question 6

How do Opiates drugs work?

Answer 6

• Increases relaxation, decrease sensitivity to pain.
• Morphine
• Heroine
• Codeine
• Mimic endorphins (naturally occurring chemicals in the brain).
• Attach to endorphins receptors
• increase dopamine
• Also blocks hindbrain area that normally release norepinephrine.
• Reduces memory storage and stress.

Question 7

How does Marijuana work?

Answer 7

• Contains cannabinoids
• Binds to specific receptors.
• Inhibits GABA release
• Increase in dopamine release
• perception of heightened awareness.
• Receptors are abundant in hypothalamus (feeding).
• increases appetite.

Question 8

How does Botox (Botulinum toxin) work?

Answer 8

• Deadly neurotoxin released by bacteria found in decaying food.
• Antagonist
• Blocks the release of acetylcholine at neuromuscular junctions - paralysis.
• But, in small doses can be used to reduce muscle tremors and cosmetically.

Question 9

What is addiction?

Answer 9

• Many addictive substances increase activity at dopamine synapses.
• Particularly in the nucleus accumbens.
• Drugs increase need for the substance even if the experience is not pleasant.
• Addiction can be hard to define, particularly when it relates to legal, socially acceptable substances.
• Addiction = continued use of a substance when it interferes with your life.
• Alcohol acts on many areas of the brain - mainly inhibitory effects.

Question 10

What is drug tolerance?

Answer 10

• Pleasurable effects decrease as addiction develops.
• can lead to increase in drug intake.
• Learned.

Question 11

What is drug withdrawal?

Answer 11

• Cravings for the drug
• Relapse causes increased sensitivity
• User learns that the drug relieves distress associated with withdrawal, and so craves it more during future withdrawal.

Question 12

What are the two types of alcoholism?

Answer 12

• Type 1:
• Late onset (afer 25)
• Gradual onset
• Equal men and women
• Less severe
• Type 2:
• Early onset (before 25)
• Rapid onset
• More men than women
• severe.

Question 13

How might Genes influence alcoholism?

Answer 13

1. Coding for an increase in risk taking behaviour.

2. Coding for an increased stress response = more likely to relapse after quitting.

Question 14

Do sons of alcoholic fathers show predispositions to to alcoholism?

Answer 14

1. Show less than average intoxication - tolerance to alcohol.
2. Show greater decrease of stress when drinking.
3. Slightly smaller amygdala (therefore increased risk taking).

Question 15

What is depression?

Answer 15

• Feelings of extreme sadness and helplessness.
• Severe enough to interfere with daily life, and can last for weeks or months rather than days.
• The absence of happiness.
• Twice as common in women than men.
• 5% adults have clinically significant depression.

Question 16

What causes depression?

Answer 16

• Life experiences or biological propensity?
• Moderate degree of heritability to depression (fu et al., 2002).
• But not specific to depression - relatives also more likely to suffer from anxiety disorders, substance abuse, bulimia.
• More common among relatives of women with early onset depression (before 30).

Question 17

What effect does Serotonin have on depression?

Answer 17

• Low serotonin turnover associated with aggression and depression.
• so genes controlling serotonin have been implicated.
• Gene controlling the serotonin transporter protein.
• This protein controls ability of an axon to reabsorb serotonin.
• Short and long types.
• If you have two short forms of the gene = more likely to have depression in response to stressful events.

Question 18

What is Bipolar disorder?

Answer 18

• Unipolar disorder: varying between normality and depression.
• Bipolar disorder: varying between mania and depression (Mania = restless activity, excitement, confidence, rambling speech).
• Increased metabolism during manic phases (PET scans)
• Possible genetic component - more common in monozygotic twins, but this seems to increase risk rather than cause.
• Treated with lithium salts
• block synthesis of arachidonic acid (associated with brain inflammation).

Question 19

What is Seasonal Affective disorder?

Answer 19

• Depression associated with one season (usually winter).
• Common near the poles where the nights are long.
• Less severe than major depression
• Light therapy as treatment (affects biological clock).

Question 20

What is schizophrenia?

Answer 20

• Split mind - but is NOT related to multiple personality disorder.
• The split refers to a division between emotional and intellectual experiences and behaviour.
• some patients show inappropriate emotional expression that seems detached from current circumstances.
• Other symptoms: hallucinations, delusions, thought disorders, movement disorders.
• can be acute or chronic.
• Not all patients exhibits all symptoms.
• Difficult to diagnose, often confused with other conditions.
• but, PET scans have found activation in in thalamus, hippocampus and auditory cortex during hallucinations
• Impairments on tasks remembering rules implies problems with the hippocampus.
• More common in men.
• Earlier onset in men.
• Present in 1% of the population (2011).
• Equal proportions in all cultures/populations (although more diagnoses in developed countries).
• More likely in closely related individuals.
• More likely in closely related individuals.

Question 21

How does schizophrenia develop?

Answer 21

• Neurodevelopmental hypothesis
• Abnormalities in the development of the nervous system before birth (prenatal) and in the newborn.
• Infections, poor nutrition, complicated delivery, BUT, only increases chance of schizophrenia slightly.
• Some slight brain abnormalities in patients, suggesting subtle changes during development.

Question 22

How is schizophrenia associated brain anomalies?

Answer 22

1. Ventricles (fluid - filled spaces in the brain) larger, so less space for brain cells.
2. Prefrontal cortex damaged (working memory impaired).
3. Cell bodies are smaller in the hippocampus and prefrontal cortex (memory consolidation and working memory).
4. Less lateralisation than most people
   - implication for language deficit
   - More likely to be left handed.

Question 23

How is schizophrenia at the level of the synapse?

Answer 23

• Abuse drugs are associated with an excess of dopamine, and can cause psychosis.
• Dopamine hypothesis of schizophrenia = excess activity of dopamine synapses.
• Schizophrenia patients have twice as many dopamine receptors than other people.
• But, normal levels of dopamine are found when measured directly.
• Schizophrenia is also associated with lower than normal release of glutamate and fewer receptors in the prefrontal cortex.
• Glutamate hypothesis of schizophrenia = deficient activity at glutamate and fewer receptors in the prefrontal cortex.
• related to dopamine - dopamine inhibits glutamate release and glutamate activates neurons than inhibits dopamine.
• Phencyclidine (PCP, angel dust) inhibits glutamate receptors and procedures similar to symptoms to schizophrenia (hallucinations, thought disorder, memory loss.