BIOPSYCHOLOGY: LECTURE 9

ACTIONS OF DRUGS ON THE NERVOUS SYSTEM

Dr Paula Trotter: Office hours Mon 12:30-15:30,

Room BR3.53
RECAP
Releasing Neurotransmitters
Action
At rest potential

Ca+ Ca+
Ca+

• Synaptic vesicles • Voltage-dependent

‘dock’ against the pre- calcium channels open
synaptic membrane • Calcium ions (Ca2+)
enter the cell
Releasing Neurotransmitters

• Calcium ions cause vesicles to fuse

with pre-synaptic membrane.

Ω
• Vesicles release neurotransmitters

The entire process

is called
exocytosis
Postsynaptic Receptors neurotransmitter

• Neurotransmitters bind to specific Receptor site

receptor sites in post-synaptic
membrane.
- ‘Lock and key’ mechanism
membrane
• They affect the post-synaptic
membrane potential by opening
ion channels. This neuro-
transmitter does not
• There are two main classes of ‘fit’ this receptor
receptor…
**1. Ionotropic Receptors Transmitter-gated
or
• Neurotransmitter receptor site on ion channel. ligand-gated channels
• Neurotransmitter causes ion channel to open or
Neurotransmitter Ions
close.
Ion
• Membrane potential of postsynaptic cell channel
Receptor
altered due to change in ion distribution. site
• Effects are direct and rapid (<1 ms) and short-
lasting (effects of decay with a half-life ~ 5 ms)

Most ionotropic effects rely on

glutamate or GABA
(most of the sensory/motor information)
2. Metabotropic Receptors
neurotransmitter
• Neurotransmitter receptor site on signal
Signal
protein that is linked to a G-protein. protein Ion channel

• Portion of G-protein breaks away, and

activates ‘second messenger’ chemicals.

• G-proteins or second messengers bind G-protein

Second
to ion channels Guanosine triphosphate messenger
GTP

• Effects are indirect, slower (~30 ms), and

longer-lasting (~several seconds). Metabotropic synapses use many NT
such as DA, NE, 5-HT,
and sometimes Glu and GABA
(taste, smell, pain, cognitive functions)
Postsynaptic Effects
Depend on which ion channels are opened
Depolarisation (Excitatory) Hyperpolarisation (Inhibitory)
e.g. sodium channels open, and Na+ e.g. potassium channels open, and K+
enters the cell. leaves the cell
Inside of postsynaptic cell becomes more Inside of postsynaptic cell becomes more
positive negative
Postsynaptic cell more likely to fire Postsynaptic cell less likely to fire.

Threshold for activation: -65mv

EPSP: excitatory postsynaptic potential IPSP: inhibitory postsynaptic potential

Ending the signal
Reuptake
Neurotransmitters transported
back into the cytoplasm of the
neuron (requires energy).
Degradation
Enzymes break down and deactivate
neurotransmitter molecules.
Autoreceptors
Action
potential
• Some receptors are found on the
presynaptic membrane. Autoreceptor
• They detect and regulate levels of
neurotransmitter in the synapse.

• They affect the amounts of

Post
neurotransmitter that are released. synaptic
receptors
The big picture

100 billion (or more!) neurons in the nervous

system.

Each neuron can communicate with

thousands of other neurons: an estimated
200 trillion synapses.

There are over a hundred different types of

neurotransmitter.

Neurotransmitters can have different effects

depending on the receptor type.
ACTIONS OF DRUGS ON THE
NERVOUS SYSTEM
Learning objectives
• Define what is meant by agonistic and antagonistic drugs.

• Describe some of the mechanisms by which agonistic and

antagonistic drugs can affect the production, release, reception,
reuptake and degradation of neurotransmitters.
• Understand the importance of drug research in the field of
biopsychology.
Key Vocabulary
 Drug
 Agonist
 Antagonist
 Precursor
 Transporter
What is a drug?
• An exogenous chemical that:

- is not necessary for normal functioning and

- significantly alters the functions of certain cells in the body
when taken in low doses.
• Includes therapeutic and ‘recreational’ drugs.

• Biopsychologists are interested in drugs that affect the

nervous system.
The sites of drug actions
• The behavioural effects of
many drugs are due to their Synthesis of enzymes
influence on synaptic neurotransmitters *
* *
communication. * *
Storage in vesicles

‘Exocytosis’
• May influence:
Regulation by
autoreceptors
- Production, storage or
release of neurotransmitters. Reuptake or
degradation of
- Pre or Postsynaptic
neurotransmitters
receptors
Binding to
- Reuptake or degradation of
postsynaptic
neurotransmitter. receptors
 • Agonists • Antagonists

• Facilitate the effect of a • Counter the effects of a

particular neurotransmitter. particular neurotransmitter.
e.g. increase the amount of e.g. decrease the amount of
dopamine released. dopamine released.

IMPORTANT: This distinction is NOT

the same as excitation vs. inhibition…
Agonists
• If the neurotransmitter has an excitatory effect…
… an agonistic drug will increase this excitatory effect

Depolarise
-65 -65

-70 -70

• If the neurotransmitter has an inhibitory effect…

… an agonistic drug would increase the inhibition

-65 -65 Hyperpolarise

-70 -70
Antagonists
• If the neurotransmitter has an excitatory effect…
… an antagonistic drug will decrease this excitatory effect

-65 -65

-70 -70

• If the neurotransmitter has an inhibitory effect…

… an antagonistic drug would decrease the inhibition

-65 -65

-70 -70
Agonistic Effects
Neurotransmitters bind to specific Agonist drug
receptor sites on the postsynaptic
neurotransmitter
membrane.

Some agonist drugs bind to the same

receptor sites as the neurotransmitter and
open ion channels.

Greater postsynaptic effect

e.g. “Valium” binds Postsynaptic neuron

to receptors for the
neurotransmitter
GABA
Chloride ions
Agonistic Effects
Neurotransmitter molecules are made from
precursors.
enzymes
Some agonist drugs may: *
- Increase the amount of precursor. * * precursors
* *
- Activate enzymes that speed up synthesis.
More neurotransmitter is made.

e.g. “L-DOPA” is the

precursor to
dopamine

https://www.youtube.com/watch?v=sf1N0Zf5IqA
Agonistic Effects
Neurotransmitter molecules are made from
precursors.
enzymes
Some agonist drugs may: *
- Increase the amount of precursor. * * precursors
* *
- Activate enzymes that speed up synthesis.
More neurotransmitter is made.

e.g. “L-DOPA” is the

precursor to
dopamine

https://www.youtube.com/watch?v=sf1N0Zf5IqA
Agonistic Effects
Neurotransmitters in the cleft can be
transporter
transported back into the presynaptic neuron
(‘reuptake) or broken down by enzymes.

Some agonist drugs block transporters or

stop the enzymes from working.

Neurotransmitters stay in cleft for

longer. enzymes

e.g. drugs that stop

acetylcholinesterase will
facilitate acetylcholine
activity
Antagonistic Effects
Neurotransmitters bind to postsynaptic
receptor sites. neurotransmitter

Antagonist drugs may block these receptor

sites Antagonist
drug
Fewer postsynaptic receptors are
activated.

e.g. “chlorpromazine”
blocks dopamine Postsynaptic neuron
receptors
Antagonistic Effects
Neurotransmitter molecules are released from
the synaptic vesicles.

Drugs that block the release of

neurotransmitters are antagonists.

Less neurotransmitter is released.

e.g. “Botox” blocks

acetylcholine at
neuromuscular junction
Antagonistic Effects

Autoreceptors detect and regulate the level of

neurotransmitter –
provides a negative feedback loop.

Some antagonist drugs stimulate these

autoreceptors.

The presynaptic neuron reduces the

amount of neurotransmitter that is
released.
e.g. “clonidine” binds to
presynaptic α2 receptors,
inhibiting further release
of adrenaline and
noradrenaline.
Agonist or Antagonist?

Agonist or
Drug Action
antagonist?

Black widow Stimulates the release of

Agonist
spider venom neurotransmitters from vesicles.
PCPA
Inactivates the enzyme needed to make
Para-chloro- Antagonist
the neurotransmitter (5-HT).
phenyl-alanine
Inactivates presynaptic transporters
Cocaine responsible for reuptake of Agonist
neurotransmitter.
Blocks (NA) autoreceptors on presynaptic
Idazoxan
membrane. Agonist
Black widow spider venom
Venom is "Latrotoxin"
Stimulates the release of neurotransmitters from vesicles.
Latrotoxin is a neurotoxin; it stimulates nerve cells to release large
amounts of neurotransmitters, (Glutamate, GABA,
norepinephrine, & acetylcholine.)

affects motor nerve endings and endocrine cells

https://www.youtube.com/watch?v=UG4VNMA8TG8
Cocaine
Inactivates presynaptic transporters responsible for reuptake of neurotransmitters.

Amphetamines and cocaine bind to — thus blocking — transporters used for the reuptake
of dopamine (and noradrenaline and serotonin) into presynaptic neurons. This causes the
level of dopamine to rise in the synapses.

The resulting chemical build-up between nerves causes euphoria or

feeling "high“ (30 min / 2 h)

an increasing sense of energy and alertness irritability

an extremely elevated mood paranoia
a feeling of supremacy restlessness
Excited, full of energy anxiety

National Institute on Drug Abuse (NIDA) (2016) Cocaine https://www.drugabuse.gov/publications/research-reports/cocaine/how-does-cocaine-produce-its-effects

Cocaine is responsible for more U.S. emergency room visits than any other
illegal drug.

Gastrointestinal tract:
- Ulcers
- Perforations

Kidneys:
- Kidney failure

Sexual dysfunction
Why do we care…
• Understand the neurochemical basis of:
• psychological functions and behaviours.

• psychological disorders.
• Develop treatments for psychological disorders.

Acetylcholine Acetylcholine
agonists improve antagonists make
memory memory worse

Memory loss can be Acetylcholine agonists

Acetylcholine
due to reduced to treat memory loss!
is involved in
Acetylcholine activity (e.g. Donezepil)
memory
A Survey of Abused Drugs
The mouse house party
• http://learn.genetics.utah.edu/content/addiction/mouse/
See how these drugs influence synaptic communication!
Some other physical effects of drugs
http://tobaccobody.fi/

http://
www.dailymail.co.uk/news/article-2589612/Shocking-images-devast
ating-physical-toll-drugs-take.html

http://
www.bbc.co.uk/news/av/uk-scotland-21843181/app-showing-ageing
-effects-of-alcohol-goes-global
 Any questions?
Reading

• Kalat, Module 3.3

• Pinel: sections 4.7

• Or relevant sections in another biopsychology textbook