Lecture 34- Drugs and the brain

Question 1

What is a common feature of the drugs that affect behaviour?

Answer 1

-often small molecules (ethanol, nicotine, heroin, valium, LSD, cocaine)

Question 2

What are the three reasons why people use recreational or abused drugs?

Answer 2

1. Pleasure -hedonic drugs are typically addictive and users exhibit tolerance along with addiction(-heroin= exhibit desensitization -shift to the pleasure from the effect to just taking the drug) 2. Novelty or unreality- psychadelic drugs are less commonly considered addictive, provide and experience that is interesting or stimulating 3. some drugs are highly addictive (tobacco) and are not associated with tolerance (no associated change in behaviour execept for seeking the drug)

Question 3

What aspects of brain function do these drugs affect?

Answer 3

1. Behaviour 2. “Mental state”: Motivation, perceived salience, meaning and significance, arousal/vigilance, hedonic experience, emotional states and experiences

Question 4

Why do these drugs work?

Answer 4

-must mimic some thing natural in our brain -the drugs must imitate neurotransmitters to have an effect -many abused drugs appear to act by modulating neurotransmission at the synapses of the diffuse modulatory systems particularly serotonin, dopamine and noradrenaline

Question 5

What are drugs with mind altering effects called?

Answer 5

-psychoactive -these can be considered hedonic, psychedelic, stimulant

Question 6

What is LSD?

Answer 6

-psychedelic drug, hallucinogen -produces distortions of sensations and abnormal associations between sensory experiences -in the 1960s and 1970s it was legal and widely promoted by users as mind expanding -probably a serotonin antagonist but its action is complex and not well understood -LSD is serotonin agonist but sth else must be involved as it doesn’t affect everything in the brain only selective

Question 7

What are stimulant drugs?

Answer 7

-amphetamines and cocaine -seem to act on aminergic transmission (noradrenaline and dopamine) -however heroin is an opiate and also modulates aminergic systems…

Question 8

Why are hedonic drugs so addictive?

Answer 8

-the uniting principle of addictive drugs appears to be that they enhance synaptic dopamine by means that dissociate it from normal behaviour control and they act to reinforce their own acquisition -modulating dopamine from VTA to accumbens -efefct on dopaergic transmission= all drugs that are addictive have this effect -increase in dopamine

Question 9

What is the action of amphetamines?

Answer 9

-

Question 10

How does cocaine work?

Answer 10

-plasma membrane dopamine uptake transporter blocker -enhances dopamine

Question 11

What is the majority of communication between neurons like?

Answer 11

-chemical

Question 12

What are the variations of synaptic arrangements in neurons? (4)

Answer 12

1. direct effect on a few
2. neuroendocrine transmission= vasopressin, hormones can affect big effect
3. want big effect= selective
4. single neuron of the dopamine system will make en passant connections with many other neurons
   - unusual pattern of connectivity
   - change of the state of the brain

Question 13

Why do drugs work in subtle ways?

Answer 13

-as you wouldn’t want big changes= that could lead to problems! -that is why effect on diffuse modulatory systems (metabotropic channels)

Question 14

In which diffuse modulatory systems do addictive drugs act most often?

Answer 14

-dopamine system -VTA to nucelus accumbens change is what makes drugs addictive -heroin, nicotine, cocaine…

Question 15

What can paranoia be a side effect of?

Answer 15

-common in schizophrenic illness -side effect of medication or recreational drugs such as marijuana, and particularly stimulants such as methamphetamine and crack cocaine

Question 16

What drug is the most abused in the world?

Answer 16

-alcohol

Question 17

How many users of alcohol are there worldwide?

Answer 17

2 billion

Question 18

How many deaths does alcohol cause per year?

Answer 18

-3.2% of deaths -and 4% of total years of life lost

Question 19

What is the annual cost of alcohol caused problems in Australia?

Answer 19

-4.5 billion dollars (2.6 times more than all other drugs, illicit) -about 2/3 of the cost are alcohol dependence-related -1/3 is the immediate effect

Question 20

What are the impacts of drinking? (diagram)

Answer 20

• what is in drinking and the outcome
• depends how much you drink, the pattern

Question 21

What are the chronic alcohol related diseases? (5)

Answer 21

1. cancer (mouth and oropharyngeal, esophageal, liver, breast) 2. neuropsychiatric diseases (AUDs, unipolar major depression, epilepsy) 3. diabetes, cardiovascular diseases (metabolic disturbance) 4. gastrointestinal diseases (cirrhosis of the liver) 5. conditions arising during the perinatal period

Question 22

What are the two chronic alcohol related diseases that are more brain related? (2)

Answer 22

1.neuropsychiatric diseases (AUDs, unipolar major depression, epilepsy) 2. conditions arising during the perinatal period

Question 23

What are examples of comorbid (accompanying) condoitions to alcohol abuse?

Answer 23

1. Medical conditions such as malnutrition and diseases of the liver and the cardiovascular system 2. Neurological conditions such as head injury, inflammation of the brain (i.e. encephalopathy) and fetal alcohol syndrome 3. Psychiatric conditions such as depression, anxiety, post traumatic stress disorder, schizophrenia and the use of other drugs -lot of diseases because of alcohol -lot of the problems come from the damage to liver then causes other damage -now there is evidence to actual damage by alcohol to neurons

Question 24

What is the mechanistic action of ethanol?

Answer 24

• ethanol is active at the GABA A receptor
• chloride channel opened by GABA
• ethanol also agonist and antagonist not clear
• depressive and stimulant
• know a lot about small picture and big picture but cannot link very well

Question 25

What does alcohol do to GABA receptors?

Answer 25

-both potentiates it and antagonises GABA's effects (which can be used to explain sedation and disinhibition -chronic alcohol consumption decreases GABA receptor density in the brain= which is consistent with anxiety (and the use of benzodiazepine) in alcohol withdrawal

Question 26

Does alcohol interfere with glutamate action?

Answer 26

-yes -chronic alcohol consumption increases glutamate receptor sites in the hippocampus an areas crucial to memory

Question 27

What is the relationship between alcohol and serotonin and endorphins?

Answer 27

-alcohol directly stimulates release of the neurotransmitter serotonin which is important in emotional expression and of the endorphins natural substances related to opioids, which may contribute to the "high" of intoxication and the craving of the drink

Question 28

What is the relationship between alcohol and dopamine?

Answer 28

-alcohol leads to increase in dopamine (DA) a neurotransmitter that plays a role in motivation and in the rewarding effects of alcohol

Question 29

What are the acute effects of alcohol? (5)

Answer 29

1. potentiation and antagonisation of GABA receptors, chronic alcohol= decrease in density of GABA receptors 2. increase in glutamate receptor sites in the hippocampus 3. stimulates serotonin release 4. stimulates endorphin release 5. stimulates dopamine release

Question 30

What are the chronic effects of alcohol? -neuropathologically

Answer 30

1: alcoholics have smaller brain weight 2. reduction in brain volume = mainly white matter loss but also grey matter and neuronal loss 3. microscopically there are no obvious white matter lesions in the cerebral hemispheres of uncomplicated alcoholics (those not showing liver damage) 4. much of the damage is exacerbated by thiamine (B1) deficiency and used to be thought that it was the main reason for brain damage in alcoholics but now even non complicated alcoholics have damage so not the whole picture

Question 31

Where is the loss of neurons when chronic alcohol consumption?

Answer 31

-neuronal loss in specific regions of the cerebral cortex = superior frontal association cortex -hypothalamus -cerebellum -mostly frontal and prefrontal damage -cerebellar damage= the ataxic gait

Question 32

What is the comparison of the brain of an alcoholic and non alcoholic?

Answer 32

-younger alcoholics= changes in brain volume across the board -old alcoholic= biggest change in prefrontal -posterio temporal seems unaffected in both, not clear why -the old alcoholic looks like alzheimer's patient brain

Question 33

Can ethanol get through the blood brain barrier and through the placental barrier?

Answer 33

-complications with alcohol in prenatal developmemnt -blood brain barrier: ethanol can get through as it is small and partly lipid soluble -also can get through the placental blood barrier into the developing fetus

Question 34

What are the external features associated with FAS (fetal alcoholic syndrome)? face (9)

Answer 34

1. small head 2. low nasal bridge 3. small eye openings 4. short nose 5. thin upper lip 6. underdeveloped jaw 7. smooth philtrum 8. flat midface 9. epicanthal folds (like my eyes)

Question 35

What are the external features associated with FAS (fetal alcoholic syndrome)? hands

Answer 35

-simian crease

Question 36

What are the FAS symptoms developmentally?

Answer 36

-developmental neural disorder -complex pattern of behavioural or cognitive abnormalities inconsistent with development level -learning disabilities -academic achievement -impulse control -social perception -communication -abstraction -math skills -memory -attention and judgement -general cognitive deficits = IQ score at or below the 3rd percentile

Question 37

What did the autopsies of infants with FAS show?

Answer 37

-extensive brain damage, microcephaly, migration abnormalities, callosal dysgenesis and a massive neuroglial leptomenigeal heterotopia covering the left hemisphere(structures where they shouldn't be ) -severe hydrocephalus (expansion of the ventricles and skull), abnormal neural migration and a small corpus callosum and cerebellum

Question 38

Takehome message?

Answer 38

- little agents can have big effects, these effects are coherent, why doesn't it affect the whole brain? something missing - serotonin is correlated with mood but is not mood, among other things mediates part of it -dopamine antagonists are effective in treatment of schizophrenia but dopamine is not the neurotransmitter for thought - dopamine and noradrenaline agonist have powerful effect on behaviour and motivation but dopamine is not the producer of reward or pleasure