Psychopharmacology - intro

Question 1

what is Psychopharmacology

Answer 1

-the study of the effects of drugs on cognition, mood and behaviour (i.e their psychoactive properties)

Question 2

drugs can only have psychoactive properties if..

Answer 2

if they interact with existing endogenous neurochemical
processes in the brain.

so they interfere with processes we already have

Question 3

endogenous

Answer 3

generated from inside, already existing, drugs interfere with these processes

Question 4

why study psychopharmacology/ types of psychopharmacological research

Answer 4

Drugs can be used as ‘probes’ to study functions of endogenous
neurotransmitter systems (NTs).
(understand systems better)

– Investigation of drug effects can also lead to development of
treatments for medical/psychological conditions (Alzheimer’s,
schizophrenia, depression, etc.).

Question 5

two themes in psychopharm research

Answer 5

1. Research is difficult!
   – Evidence needs interpreting, critically.
2. We only know what we happen to have found
   out so far.
   – Methods aren’t perfect, and many discoveries come
   about by chance.

Question 6

what is important in the methodology for studying drug effects

Answer 6

-we need to know what a drugs effects actually are , so as with most science , we need to compare with the effects in a control condition

Question 7

what is a confound

Answer 7

A confound is a potential alternative cause of what appears to
be a drug effect

Question 8

in what cases can confounds be controlled in

Answer 8

Natural recovery.
(they could recover over time naturally?)
– Control by: comparison with no-treatment group.

• Expectation of drug effect.
  – Control by: comparison with placebo condition (e.g., sugar pill)
  and ensure “blinding” of conditions.
• Expectation can still occur with placebo controls if side-
  effects (or other drug effects) lead to correct guessing of
  participant’s condition (“unblinding”).
  – Control by: comparison with an active placebo condition (e.g.,
  another drug with similar noticeable effects)

Question 9

types of drug studies
-randomised controlled trials
-open label trials
-‘blinding’ of conditions, when can unblinding occur

Answer 9

Randomised controlled trials – RCTs:
* These trials involve a control condition (e.g. placebo, but could
be e.g. current best treatment) and random assignment of
participants to groups.

Open-label trials:
* Studies without blinding are referred to as being open-label.
(There may still be a comparison with a control group, e.g.
placebo).

“Blinding” of conditions:
– blind = participant unaware of group assignment;
– double-blind = participant and researcher unaware of group
assignment.
– N.B., “unblinding” can occur when effects are detectable.

Question 10

types of drugs studies
between subjects
within subjects , crossover design, washout period

Answer 10

Between-subjects design:
* The comparison is between participants: drug group [participants 1,
3, 5…] versus control group [participants 2, 4, 6…]

Within-subjects designs:
* The comparison is between conditions for the same participants: drug
condition [participants 1, 2, 3… when receiving drug] versus control
condition [participants 1, 2, 3… when receiving e.g. placebo]
(at one point a participant will have a drug and at another point have a placebo)

• For instance, a crossover design. (E.g., “AB/BA” : drug-then-control
  / control-then-drug.
  half participants have a drug first and few wakes later have a placebo , vice versa)
  A “washout period” may occur between
  treatments-taking the drug a few weeks later)

Question 11

effects in drug vs placebo groups
khan et al study

-what does the change in placebo groups indicate?
-how do we conclude the effect of the drug treatment?

Answer 11

• N.B., % change in placebo group will include any natural time-course of condition
  as well as expectancy effect of placebo. (No no-intervention group for comparison).

-The effect of drug treatment is difference between drug & placebo groups

Question 12

measures of drug effects
-why be careful when using subjective measures?

Answer 12

Changes in subjective experience (‘phenomenology’) & mood (self-
report alertness, happiness, anxiety, etc.)

• Changes in physiological activity (fMRI, EEG, etc.)
• Changes in task performance (simple & choice RT tasks, vigilance
  tasks, memory, problem solving, etc.)
• Changes in behaviour (social co-operation, aggression, hyperactivity,
  etc.)

─ N.B., subjective measures (e.g. ratings by self or researcher) can be
susceptible to bias or expectancy – hence double-blind technique.

Question 13

what is a neurocognitive model
-what could the model be

Answer 13

a neurocognitive model aims to explain the relationship between specific neurotransmitter systems, cognitive processes and subjective experiences

The model could be of a type of drug effect
(stimulant, sedative, psychedelic, etc.)

• Or it could be of a neuropsychiatric conditions
  (ADHD, depression, schizophrenia, etc.)
  -3 way connection

Question 14

examples of neurocognitive models

Answer 14

noradrenaline

Question 15

components of the neuron and synapse
-dendrite
-cell body
-axon
enzymes and synthesis
synapse

Answer 15

• Dendrites receive chemical signals (neurotransmitters, NTs) from other neurons.
• The cell body (soma) includes the nucleus, which controls cell’s activity.
• The axon allows an electrical signal (action potential) to travel to axon terminal.
• Enzymes control synthesis of neurotransmitters, which are stored in vesicles and
  released from the axon terminal.
• The signal is transmitted between neurons at the synapse

Question 16

how is an action potential generated
-axon hillock

Answer 16

Multiple excitatory & inhibitory signals (‘post- synaptic potentials’;
PSPs) are integrated (combined) to determine whether an action potential is generated axon hillock: action potentials are triggered here if sufficient depolarisation (+ relative to -)

Question 17

• Excitatory signals ________ the likelihood of receiving neuron
  producing action potential
  – Inhibitory signals ________ the likelihood of receiving neuron
  producing action potential

Answer 17

Excitatory signals increase likelihood of receiving neuron
producing action potential

– Inhibitory signals decrease likelihood of receiving neuron
producing action potential

Question 18

endogenous processes involving neurotransmitters

Answer 18

(1) synthesised by enzymes
& packaged in vesicles

(2) released,
then bind with
postsynaptic
receptors

(3) deactivated:
presynaptic reuptake or
broken down by
enzymes

Question 19

the NT has to _______ to be able to produce an effect

Answer 19

fit the receptor (like a key in a lock)

Question 20

what are the effects of the NTs at the post synaptic cell

Answer 20

NTs influence the opening and closing of post-synaptic ion channels. This
allows electrically charged ions to move in or out of the post-synaptic cell,
making it more or less likely to ‘fire’ (produce an action potential).

• Some NTs have less direct effects, e.g. modulating the effect of other NTs on
  ion channels, or leading to other synaptic changes (e.g. for learning)

Question 21

the effect of a neurotransmitter depends on _____

Answer 21

receptor type
NTs therefore have different
effects at different receptors (e.g. nicotinic and muscarinic ACh receptors)

Question 22

explain NT deactivation

Answer 22

NT detaches from receptor &
is then:
* transported back into the pre-
synaptic neuron (reuptake)
or

• broken down by enzymes in
  the synaptic cleft (products of
  enzymatic breakdown may
  then be recycled)

Question 23

how do drugs work
-what can they influence
-agonists
-antagonists

Answer 23

Psychoactive drugs interact with NT systems.

• Drugs can influence NT synthesis, storage, release,
  receptor interactions, and/or deactivation.
• Drugs can have agonistic effects, where they mimic or enhance the effects of a NT.
• Drugs can have antagonistic effects, where they
  block or reduce the effects of a NT.

Question 24

what are some ways which drugs interfere with endogenous processes

Answer 24

synthesised by enzymes
& packaged in vesicles
(1)
 synthesis (e.g. more precursor;
L-dopa – see Lecture 3)

(2) released,
then bind with
postsynaptic
receptors
 binding (e.g. block
receptor; ketamine – see
Lecture 1)

(3) deactivated:
presynaptic reuptake or
broken down by
enzymes
 deactivation (e.g.
block reuptake; SSRIs
– see Lecture 4)

Question 25

two major neurotransmitters
glutamate and gaba

Answer 25

-glutamate and GABA work in opposition to each other to maintain the right balance between inhibition & excitation.
Both are found throughout the brain.

Question 26

what are
glutamate
GABA

Answer 26

Glutamate (glutamic acid) is the main excitatory NT, released by ~ 50% of neurons.
It is a precursor for GABA.

• GABA (gamma-amino-butyric acid) is the main inhibitory NT, released by ~ 40% of neurons. It is synthesised from glutamate.

Question 27

Gaba agonists
-what do they do
-examples, what are they commonly used for

Answer 27

Benzodiazepines (BZDs), barbiturates & alcohol
enhance the inhibitory effects of GABA and are:
– anxiolytic (reduce anxiety).
– sedative (reduce arousal / increase relaxation).
– hypnotic (promote sleep)

BZDs (diazepam, temazepam, lorazepam, etc.) are commonly
prescribed for anxiety and are also used as pre-anaesthetic
relaxants in surgery.

• Barbiturates are more potent GABA agonists – mainly
  used as general anaesthetics, to induce coma (e.g. after
  brain injury), & to treat epilepsy.

Question 28

Gaba antagonists
what do they do and how
examples

Answer 28

-reduce the inhibitory effects of gaba (inhibit action of gaba)

flumazenil – blocks BZD site on GABA receptor; reverses BZD
sedation (e.g. after medical operation); antidote for BZD overdose

• picrotoxin – stimulant (increases arousal); convulsant (induces
  epileptic seizures at high doses); antidote for barbiturate overdose

Question 29

glutamate agonists
-what do they do
-example

Answer 29

-enhances glutamates excitatory effect
glutamate agonists (e.g. ibotenic acid, found in poisonous
mushrooms) are excitotoxic – i.e. can kill nerve cells through
over-excitation

Question 30

glutamate antagonists
-what do they do
-examples

Answer 30

-blocks binding of glutamate so blocks excitatory effect of glutamate
-ketamine = NMDA receptor antagonist; blocks excitatory
effects of glutamate, used medically as sedative & anaesthetic.

Question 31

glutamate has various receptor ____ ______.
-what is NMDA important for

Answer 31

-sub types
-is important in initiating the long-term synaptic changes necessary
for learning & memory.

– is also implicated in drug addiction, schizophrenia & epilepsy.