Psychopharmacology

Question 1

synaptic sequence

Answer 1

• Strong stimulation leads to impulse (action potential)
• The action potential is propagated further down the axon
• When the action potential reaches the axon terminal, this initiates synaptic transmission

Question 2

the role of Ca2+ in synaptic transmission

Answer 2

• When the action potential reaches the axon terminal, it opens Ca2+ voltage-gated channels
• Ca2+ has higher concentration outside, hence the concentration gradient pushes it into the cell
• Ca2+ ions have a specific property: they interact with neurotransmitter vesicles (storage), pushing them towards the membrane

Question 3

synaptic transmission

Answer 3

• Once the vesicles containing the neurotransmitter reach the membrane, they open up and the neurotransmitter is released into the “synaptic cleft”
• The neurotransmitter then binds to its receptors in the postsynaptic neuron. If these receptors are themselves ion-channels, they open when the neurotransmitter interacts with them
• If the receptors are not ion channels, they interact with specific ion channels and eventually open them
• As a consequence, ions enter the postsynaptic neuron, resulting in a Post-Synaptic Potential

Question 4

ntm inactivation and recycling

Answer 4

1. Diffusion: the transmitter is “lost” in the inter-cellular space
2. Enzymatic degradation: enzymes break down the transmitter
3. Re-uptake (uptake): the transmitter is recycled either in the pre-synaptic or the post-synaptic neuron. This is the most economical way to inactivate the transmitter: saves synthesis resources

Question 5

how can substances influence the different phases of the synaptic sequence

Answer 5

• Some act as early as the propagation of the action potential
• Others may influence the release of the transmitter
• Others modulate how the transmitter interacts with the post-synaptic channels (receptors)
• Finally, some alter the presence of the transmitter in the synapse by modulating its inactivation and recycling

Question 6

how do some chemicals interfere with signals going through the axon?

Answer 6

• By blocking sodium channels in the axon’s membrane (e.g. tetrodotoxin, or TTX - toxin is found in certain species of fish)
• TTX can produce paralysis of the diaphragm and death due to respiratory failure (over 10,000 times deadlier than cyanide…)

Question 7

how do substances interfere with the release of transmitter?

Answer 7

• The tetanospasmin toxin interferes with the vesicles of the neurotransmitter GABA fusing with the cell membrane
• This reduces the amount of GABA released into the synapse
• Because GABA is an inhibitory neurotransmitter this results in an imbalance between excitation and inhibition neural signals
• This leads to very strong uncontrollable muscle contractions (tetanus) which can be lethal

Question 8

excitaroty synapses

Answer 8

glutamate

Question 9

inhibitory synapses

Answer 9

GABA

Question 10

mainly excitatory, but also inhibitory synapses

Answer 10

Ach

Dopamine

Question 11

substances interfering with the release of tm - Ach

Answer 11

• Acetylcholine is a neurotransmitter that has two types of receptors: nicotinic (excitatory) and muscarinic (inhibitory)
• Botulinum toxin (formed by bacteria in improperly canned food) interferes with the release of Acetylcholine at nicotinic synapses, by preventing the vesicles from fusing with the cell membrane
• This toxin is used in the cosmetic agent BOTOX, used to treat wrinkles by reducing synaptic effectiveness at the neuromuscular junction in facial muscle

Question 12

how do substances enhance the release of transmitter?

Answer 12

• Amphetamine is very similar in structure to the neurotransmitter dopamine
• Due to its similarity to dopamine, amphetamine can enter the dopamine-releasing neuron either directly through the membrane or by binding to the dopamine transporter (molecule that ‘recycles’ dopamine back into the cell from the synaptic cleft)
• Once inside the cell, amphetamine facilitates the release of dopamine from the vesicles when these fuse with the membrane

Question 13

dopaminergic pathways

Answer 13

• Amphetamine and other drugs (cocaine, heroin, marihuana) have a profound effect on dopaminergic pathways in the brain
• One pathway is seen as particularly crucial in explaining the potent effects of these drugs: the projections from the Ventral Tegmental Area (VTA, group of cells in brain stem) to Nucleus Accumbens (group of cells in Basal Ganglia)
• VTA and Nucleus Accumbens are thought to be involved in pleasure, reward and motivation

Question 14

how do substances alter how the tm interacts with the receptors - e.g. Curare

Answer 14

• Certain substances simply bind to receptors (blocking the way of the neurotransmitter) but without opening the channel
• E.g. the plant toxin curare in South America occupies acetylcholine’s receptors in excitatory (nicotinic) synapses, blocking them and causing paralysis
• Curare here acts as an antagonist (occupies channel, but does not open it, i.e. blocking)
• Curare is used in surgery as an anaesthetic agent

Question 15

how do substances alter how the tm interacts with the receptors - agonists

Answer 15

agonists imitate the behaviour of the neurotransmitter, thus increasing its effect

heroin

marijuana

anandamide

tobacco

Question 16

heroin

Answer 16

is an artificially modified form of morphine (contained in opium)
- Heroin is an agonist of endorphins - natural body chemicals that bind to opiate receptors and reduces pain and induces relaxation

Question 17

marijuana

Answer 17

contains THC, an agonist of anandamide- natural body chemical which binds to cannabinoid receptors

Question 18

anandamide

Answer 18

involved in emotion, pain, appetite and memory

Question 19

tobacco

Answer 19

contains nicotine, which stimulates nicotinic receptors (it is an agonist for acetylcholine)

this has a short-lived generalised excitatory effect, e.g. it increases blood adrenaline level

Question 20

how do drugs influence tm inactivation and recycling?

Answer 20

• The reuptake of neurotransmitters into the original cell is done by specialised proteins: transporters
• Cocaine blocks the transporter of noradrenaline and dopamine, thus interfering with their re-uptake and boosting their effect

Question 21

chocolate

Answer 21

found to contain several psychoactive compounds

anandamide

phenylethylamine

however, chocolate contains these in such small amounts that it would not cause a noticable effect (e.g. to obtain an effect similar to that of marijuana, one would have to consume half of their body weight in chocolate!)

Question 22

anandamide - chocolate

Answer 22

the neurotransmitter produced naturally by the brain, whose agonist is THC (contained in cannabis)

Question 23

phenylthylamie

Answer 23

a compound closely related to amphetamine

Question 24

coffee/caffeine

Answer 24

• Many of the neurons that release substances like dopamine and adrenaline (catecholamines) also release a self-inhibiting transmitter- adenosine
• Adenosine binds to its receptors in the pre-synaptic neuron and inhibits the release of catecholamines
• Caffeine competes with adenosine for its receptors (it is an antagonist), blocking adenosine and thus reducing its inhibitory effect
• Caffeine also has a non-synaptic effect in neurons
• It acts on cyclic adenosine monophosphate (cAMP)
• cAMP controls the energy levels in the cell via the regulation of glucose metabolism
• Caffeine inhibits the enzyme that breaks down cAMP, thus increasing glucose metabolism in cells

Question 25

low doses of alcohol

Answer 25

Alcohol is an agonist of the neurotransmitter GABA.

GABA is typically found in inhibitory synapses.

Thus, alcohol increases the effectiveness of these synapses, leading to a feeling of relaxation.

Alcohol indirectly stimulates dopamine release.

Dopaminergic synapses in certain parts of the brain are associated with reward pleasure and positive motivation (nucleus accumbens and other structures in basal ganglia), hence the euphoria when alcohol is consumed in small to moderate doses.

Question 26

alcohol in moderate amounts

Answer 26

also indirectly increases the release of endorphins

Question 27

alcohol in high doses

Answer 27

the binding of alcohol to GABA channels leads to powerful inhibition and sedation
- In very high doses alcohol leads to the destruction of cell membranes and, hence, to brain cell death

Question 28

anxiety and GABA

Answer 28

• Anxiety disorders are in part characterised by deficits in GABA-ergic transmission
• Benzodiazepines (e.g. valium) are GABA agonists used to treat anxiety disorders
• Although their effect may seem similar to that of alcohol, they bind to different sites on GABA receptors
• They also do not bind to the same receptor sites as GABA itself: such an action is one of a non-competitive agonist

Question 29

depression

Answer 29

• Depression is associated with reduced monoamine (serotonin, dopamine, noradrenaline) transmission
• MAO Inhibitors: interfere with the enzyme MAO, which breaks down serotonin, dopamine and noradrenaline
• Tricyclic Antideressants: inhibit the transporter of serotonin, dopamine and noradrenaline

Question 30

depression and serotonin

Answer 30

• However, it has been found that serotonin is in fact the neurotransmitter closely linked to depression and less so dopamine and noradrenaline
• Selective Serotonin Reuptake Inhibitors (SSRI, e.g. Prozac): inhibits the transporter of serotonin without affecting other neurotransmitters (e.g. dopamine)

Question 31

schizophrenia and dopamine

Answer 31

• Schizophrenia is associated with a surplus of dopamine
• Its symptoms include paranoia and hallucinations
• Neuroleptics (e.g. Haldol): anti-psychotic drugs that block the transmission of dopamine by binding to dopamine receptors without opening ion channels. They are dopamine antagonists.

Question 32

cocaine

Answer 32

Blocks the transporter of noradrenaline and dopamine, thus interfering with their re-uptake and boosting their effect

Question 33

metamphetamine and amphetamine derivatives

Answer 33

• As Cocaine, these substances reduce the transport of monoamine neurotransmitters (dopamine, noradrenaline, serotonin)
• In addition, they also attach to enzymes that break down these neurotransmitters
• The overall effect is a boost in neurotransmitter transmission
• By increasing dopaminergic transmission they can induce schizophrenia-like symptoms