Neurotransmission and Psychopharmacology

Question 1

what is the synapse?

Answer 1

• Allows information to be passed (transmitted) from one neuron to the other
  
  • Information travels in one direction
  • Conduit of information from one neuron to another
  • Information travels in one direction
    ○ In deep sleep can be said to reset itself- go in both directions.
  • Junction between the terminal button of an axon and the membrane of another neuron
    ○ Occur on the terminal buttons
    No contact between the neurons (space between each neuron)

Question 2

what is the significance of the presence of mitochondria within the synapse?

Answer 2

• Presence of mitochondria within synapse suggests it needs energy.
  
  • Mitochondria= produced ATP (energy)
    ○ Allows for movement of the neurotransmitter.
    Neurotransmitter doesn’t go into the postsynaptic cell but binds with the receptors

Question 3

what is the structure of the synapse?

Answer 3

• In dendritic spines
• Presynaptic axon
  ○ Terminal containing neurotransmitters , mitochondria and other organelles
  § Help shape the neurotransmitter
  
  • Postsynaptic ending
    ○ Receptor sites for neurotransmitters
  • Synaptic cleft
    Some neurotransmitters and made in the cell body/nucleus and others in the terminal buttons.
    vesicles are released into the synaptic cleft.

Question 4

what is the first stage of synaptic transmission?

Answer 4

1. Action potential arrives at axon terminal triggering Ca2+ ions to move into cell
   Leads to an influx of calcium

Question 5

what is the second stage of synaptic transmission?

Answer 5

2. Ca2+ ions cause the migration of vesicles (which contain NTs) to the pre-synaptic membrane
   
   • Causes the vesicles to move to the end of the terminal button- once stuck to the membrane they pop.
     Tension causes neurotransmitter to enter synaptic cleft.

Question 6

what is the third stage of synaptic tansmission?

Answer 6

3. The vesicles fuse to pre-synaptic membrane and break open emptying their neurotransmitters into the synaptic cleft
   
   • Lock and key= fit into specific receptors perfectly.
     Drugs can mimic effect by being similar in shape to neurotransmitter.

Question 7

what is the fourth stage of synaptic transmission?

Answer 7

4. Neurotransmitters diffuse across the synaptic cleft towards the post-synaptic membrane
   Fit into receptor sites in postsynaptic neuron

Question 8

what is the fifth stage of synaptic transmission?

Answer 8

5. Neurotransmitters bind to receptor sites on the post-synaptic membrane with ‘lock and key’ specificity – specific NT binds to specific receptors
   Neurotransmitters don’t then enter the postsynaptic neuron, once they are bound to the receptor, they open up channels that contain all the ions and diffuse/ electrostatic pressure either moves them in our out of the cell.

Question 9

what is the sixth stage of synaptic transmission?

Answer 9

This binding opens NT-dependent ion channels which change the excitability of the post-synaptic cell.

Question 10

what is synaptic transmission?

Answer 10

the process by which one neuron communicates with another.

Question 11

what is direct postsynaptic receptors?

Answer 11

(ionotropic)
* Binding site for a NT
* Ion channel opens when NT molecule
binds
* Can act directly= inotropic response
Neurotransmitters bind to receptor channels

Question 12

what are indirect postsynaptic recpetors?

Answer 12

(metabotropic)
* Only a binding site for a NT
* Activates enzyme
* Ion channel opens elsewhere
* Metabotropic=indirect effect of neurotransmitter
* Neurotransmitter send messages to G protein
Broken down metabolite opens the receptor leading to an influx of ions.

Question 13

what is the postsynaptic potential?

Answer 13

• Graded potential- can help reach the threshold of the action potential.
  Postsynaptic potential = ions move across post synaptic membrane and alter the membrane potential

Question 14

what is depolarisation of the postsynaptic potential?

Answer 14

(excitatory) = increased likelihood of AP
○ Start off the action potential if enough comes together
Influx of sodium

Question 15

what is hyperpolarisation of the posysynaptic potential?

Answer 15

(inhibitory) = decreased likelihood of AP
○ Outflux of potassium
* Depolarisation > threshold (-55mV) triggers AP

Question 16

what does depolarisation/ hyperpolarisation epend on in the postsynaptic nueron?

Answer 16

Depolarisation/ hyperpolarisation depends on where neurotransmitter binds and what with (type of channel).
chemical to elctrical impulse
* Depends on which type of ion channel in the postsynaptic membrane is opened by the neurotransmitters
* Can open one of 3 channels:
○ Sodium - Na+
○ Potassium - K+
○ Chloride - Cl-

Question 17

what are NA+ channels?

Answer 17

• Produce excitatory postsynaptic potentials
  
  • Causes sodium to influx into the cell
  • Causes the resting potential to increase to -55mV
    ○ Increase in positive ions
    ○ Depolarisation of the cell
    ○ Increases the likelihood of action potential being released
    § Depends on depolarisation of other channels.
  • Binding cites is attached to by the neurotransmitter and opens the channel

Question 18

what are K+ channels?

Answer 18

• K+ rushes out- leads to hyperpolarisation
  ○ Decreases likelihood of action potential being released.
  Produced inhibitory postsynaptic potentials
  1. k+ channels open
  2. k+ leaves neuron
  3. hyperpolarisation reduces AP liklihood

Question 19

what are Cl- channels?

Answer 19

• At rest balance of Cl- in intra and extracellular fluid
  Leads to an influx within the postsynaptic cell
  at rest:
  1. cl- channel opens -> nothing happens as the forces are balaned

depolarisation
cl- channel opens -> cl- enters neuron -> stabilisation reduces the liklihood of AP

Question 20

what are the who ways in which neurotransmitters act?

Answer 20

1. excitatory: help propagate AP
   e.g.: glutamate
2. inhibitory: reduced AP liklihood
   e.g.: GABA

Question 21

what are the main neurotransmitters?

Answer 21

1. acetlycholine (ACh)
2. dopamine (monoamine)
3. seretonine (monomanie)
4. norepinephrine (noradrenaline) (monomaine)
5. glutamate
6. GABA (gamma-aminobutryic acid)
7. endorphins (mood enhancers)

Question 22

what is acetylcholine (ACh)?

Answer 22

• Mostly excitatory
  ○ Regulates heart rate and digestion
  
  • Found in peripheral & central NS
  • PNS: neurons controlling muscle contraction, excretion of certain hormones
  • CNS: widespread - role in REM sleep, sexual desire, activating cerebral cortex, learning, memory
  • Alzheimer’s disease is associated with a lack of ACh in certain brain regions
    ○ Due to imbalances within acetylcholine.
  • Centre of motivation
    Can inhibit the inhibitory part of the frontal cortex.

Question 23

what is the monoamine seretonin?

Answer 23

• Excitatory or Inhibitory
  ○ Can be both
  
  • Cell bodies of neurons in midbrain, pons, medulla
    ○ Below the forebrain- joining it with the hindbrain
    ○ Regulatory purpose
  • regulates mood, sleep patterns, libido, anxiety, appetite and pain.
  • imbalances include seasonal affective disorder, anxiety, depression, impulsivity, fibromyalgia, and chronic pain.
  • Medications that regulate serotonin and treat these disorders include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
    ○ Used to regulate it
    ○ Reuptake of serotonin in the synaptic cleft- more lasting effect.

Question 24

what is the monoamine dopamine?

Answer 24

• Excitatory or Inhibitory
  ○ Dual processes
  
  • Neuron cell bodies in mid brain
  • Reward system including feeling pleasure, heightened arousal, and learning.
  • Dopamine also facilitates focus, concentration, memory, sleep, mood and motivation.
  • Dysfunctions of the dopamine system include Parkinson’s disease, schizophrenia, bipolar disease, restless legs syndrome and attention deficit hyperactivity disorder (ADHD).

Question 25

what is the monoamine epinephrine?

Answer 25

(aka adrenaline) and Norepinephrine ○ Adrenaline/ noradrenaline * Epinephrine= only when sympathetic system is activated (flight or fight) * Found in peripheral NS (autonomic NS) & CNS (pons & medulla) * Also released into blood (as a hormone), causing blood vessel contraction & increased heart rate ○ Is also a hormone. ○ Particularly in extreme situations * Responsible for “fight-or-flight response” to fear and stress. * Found in peripheral NS (autonomic NS) & CNS (pons & medulla) * Important for attentiveness, emotions, sleeping, dreaming & learning * Also released into blood (as a hormone), causing blood vessel contraction & increased heart rate * Stimulates body’s response by increasing heart rate, breathing, blood pressure, blood sugar, blood flow to muscles, heightened attention and focus. ○ Sympathetic nervous system processes. * Excess epinephrine can lead to high blood pressure, diabetes, heart disease and other health problems. ○ Reciprocal effects of the above conditions. * As a drug, epinephrine is used to treat anaphylaxis, asthma attacks, cardiac arrest and severe infections * Role in mood disorders ○ e.g., bipolar disorder

Question 26

what is the peptide endorphins?

Answer 26

pain relievers ○ play a role in perception of pain. ○ “feel good” feelings. * Released by hypothalamus and pituitary gland * inhibitors (opioid receptors) Low levels of endorphins may play a role in fibromyalgia and some types of headaches.

Question 27

what is the amino acid glutamate?

Answer 27

* Most common excitatory neurotransmitter * Indirectly has excitatory and inhibitory regulations * Used by brain to synthesis GABA * Most abundant neurotransmitter in brain * Key role in cognitive functions like thinking, learning and memory * Imbalances in glutamate levels associated with Alzheimer’s disease, dementia, Parkinson’s, Huntington’s disease and seizures (epilepsy)

Question 28

what is the amino acid GABA?

Answer 28

* Simple in structure * Gamma-aminobutyric acid (GABA). ○ From glutamate ○ Synthesised from glutamate and vitamin B6 * The most common inhibitory neurotransmitter of the nervous system, particularly in the brain. ○ Similar regions as glutamate * Regulates brain activity to prevent problems in the areas of anxiety, irritability, concentration, sleep, seizures and depression. * Most important neurotransmitter in brain * Widely distributed in neurons of cortex * Contributes to motor control, vision, regulation of anxiety & many other cortical functions * Drugs that increase GABA in brain are used to treat epilepsy & calm trembling in Huntington’s disease

Question 29

what is regulating postsynaptic potentials?

Answer 29

* How might neurotransmitters be removed from a synapse? 3 processes in which they are taken away from the synaptic cleft- cant constantly be there as it needs clearing out.

Question 30

what are the processes in which neurotransmitters are removed from the synapse?

Answer 30

1. Reuptake: NT quickly pumped back into nearby glia or the axon terminal that released it ○ Through process of transporter proteins is taken to terminal buttons in presynaptic cell. ○ Glial cells and vesicles (synaptic vesicles) 2. Deactivation: NT destroyed (inactivated) by enzymes near receptors so its not recognized by receptor * (Acetylcholine A breaks down acetylcholine) 3. Removal: diffuses into surrounding area (e.g., blood) * Capillaries diffuse neurotransmitters into the bloodstream. So it can return back to its resting level

Question 31

what is psychopharmacology?

Answer 31

* Study of the effects of drugs on the nervous system and behaviour ○ Neurosciences overlap with rugs (psychopharmacology) * Primarily focusing on behaviours * Important field in neuroscience ○ Responsible for development of psychotherapeutic drugs to treat psychological & behavioural disorders Address imbalances to alleviate symptoms.

Question 32

what are drugs?

Answer 32

* Drugs are exogenous chemicals (definition) ○ Means they aren't manufactured within the body. * Unnecessary for normal functioning ○ Need them for medical conditions? ○ Readdress imbalance to make function work normally * Alter molecular functions of the synapse * Effects are physiological (biomolecular level- synapse takes place) or behavioural (excites or inhibits certain behaviours of the brain) * Natural vs artificial ○ Natural: opium, cannabis, heroine, ginger, cloves, turmeric Artificial: morpheme, aspirin, ibuprofen

Question 33

whata re the sites fo drug action?

Answer 33

* Site of action ○ Where drug interacts with molecules ○ Synaptic cleft/ postsynaptic or presynaptic vesicles * Drugs affecting behaviour normally affect synaptic transmission Excitatory and inhibitory.

Question 34

what is the agonist in drug and synaptic transmission?

Answer 34

* Facilitate of mimic action of a nuerotransmitter * facilitate postsynaptic effects

Question 35

what are antagonsist of drugs and synaptic trasmission?

Answer 35

* inhibit action of a neurotransmitter * block postsynaptic effect

Question 36

what are the 6 stages of the mechanisms of drug actions?

Answer 36

1. synthesis 2. storage 3. release 4. receptors 5. reuptake 6. destruction

Question 37

what is the synthesis of drug actions?

Answer 37

* Alter neurotransmitter synthesis in presynaptic neuron ○ So it cant effectively make the neurotransmitter in the first place ○ Less neurotransmitter being made in the cell organelles and vesicles. Modifies concentration in synaptic cleft * NT produced from specific precursor molecules ○ Changes through enzymatic reactions ○ Inactivate enzyme to get more in system * Enzymes required for change from precursor to neurotransmitters. Modes of alteration 1. Inactivate the enzymes (antagonist) 2. Introduce precursor molecules (agonist)

Question 38

what is the storage of drug actions?

Answer 38

* Alter neurotransmitter storage in presynaptic neuron ○ In presynaptic terminal * Modifies concentration in synaptic cleft * Transporter proteins in vesicle membranes move NT from cytoplasm into vesicles * Antagonist inactivate transporters- still neurotransmitter in the extracellular fluid. ○ Vesicles remain empty Cant release as the vesicles aren't stored with the neurotransmitter.

Question 39

what is the release of drug actions?

Answer 39

* Changes neurotransmitter release from presynaptic cell ○ Inhibit or increase the release * Modifies concentration in synaptic cleft Modes of alteration 1. Prevent release of NT (antagonist) 2. Trigger NT release (agonist) Very toxic chemical that triggers release- can be used as a medicine despite it toxicity level.

Question 40

what are the receptors of drug actions?

Answer 40

* Act on neurotransmitter receptors * Modify postsynaptic potentials * Direct agonist= influx of Na or K+ * Direct antagonist= closes receptor cites * Indirect= needs neurotransmitter and drug to open channels.

Question 41

what is the reuptake fo drug actions?

Answer 41

* Modify removal of neurotransmitters from synaptic cleft * Prevent serotonin from being reuptake into postsynaptic neuron * Work on transporter neurons. * Change neurotransmitter concentrations in the cleft * Agonists reduce or block reuptake

Question 42

what is the destruction of drug actions?

Answer 42

* Modify neurotransmitter destruction in synaptic cleft * Prevent destruction of the neurotransmitter.- inhibit the breakdown * Enzymes typically inactivate neurotransmitters (agonist) * Enzyme Acetylcholinesterase (AChE) in postsynaptic membrane deactivates Ach ○ Neostigmine: inactivates AChE - deactivates the enzymes that break it down. § Remains in synaptic cleft longer ○ ACh remains in synaptic cleft longer * Myasthenia Gravis Muscle tremors.