Lecture 10: Neurotransmission and Drugs

Question 1

Binding of Neurotransmitter to receptor

Answer 1

• NT binds to receptor
• Receptor is activated
• Like a key and lock (usually not 1:1 exclusive either way)

Question 2

Ligand

Answer 2

Molecule that binds to a receptor (key)

Question 3

Catecholamines

Answer 3

• Adrenaline, noradrenaline, dopamine
• Similar structures
• Can be either EPSPs or IPSPs depending on receptor

Question 4

Epinephrine/Norepinephrine

Answer 4

• Also called adrenaline/noradrenaline
  -General function: mobilize brain and body (fight or flight): increases arousal, respiration, blood flow to muscles, pupil dilation, and release of glucose
• Acts as both neurotransmitters and hormones based on if they are in the brain or blood
• Produced in small structures but project broadly
• Adrenaline is produced in the adrenal glands and medulla
• Noradrenaline is produced in the brain in the locus coerculeus and outside the brain in the ganglia, skin, and adrenal glands

Question 5

Locus Coeruleus

Answer 5

• Located in brain stem
• Responsible for stress, attention, and noradrenaline

Question 6

Raphe Nuclei

Answer 6

• Located in brain stem
• Responsible for arousal, pain, and serotonin

Question 7

Superior Colliculus

Answer 7

• Located in brain stem
• Responsible for vision

Question 8

Inferior Colliculus

Answer 8

• Located in brain stem
• Responsible for hearing

Question 9

Ventral Tegmental Area (VTA)

Answer 9

• Located in brain stem
• Responsible for dopamine, motivation, and arousal

Question 10

Substantia Nigra

Answer 10

• Located in brain stem
• Responsible for movement and dopamine

Question 11

Dopamine

Answer 11

• Involved in movement, reward-seeking, and motivation
• Produced in the substantia nigra and ventral segmental area (VTA)

Question 12

Dopamine Receptors

Answer 12

• Has D1 and D2 receptors with different roles
• Two locks opened by the same key

Question 13

Serotonin (5-HT)

Answer 13

• “Happiness neurotransmitter”
• Also involved in sleep and appetite
• Anti-depressant drugs increase serotonin
• Produced in the raphe nuclei
• Can be EPSP or IPSP

Question 14

Opioids

Answer 14

• Endorphins and enkephalins
• “Natural morphine”
• Released in happiness, laughter and euphoria
• Also in pain reduction and reward
• Mixed EPSP and IPSP

Question 15

Nitric Oxide

Answer 15

• “Reverse neurotransmitter”
• Soluble gas (NO) in dendrites
• Generated by postsynaptic enzyme in response to neurotransmitter
• Leaks out of dendrite
• Enters presynaptic neuron
  - Needs no membrane receptor
• “Retrograde signaling”
• Influences pre-synaptic mechanisms of neurotransmission

Question 16

Agonists

Answer 16

Turns on neurotransmitter system (EPSP or IPSP)
- Presynaptic: Release neurotransmitter
- Postsynaptic: Activates receptor

Question 17

Antagonists

Answer 17

Turns off neurotransmitter system
- Presynaptic: Prevents release
- Postsynaptic: Blocks receptors

Question 18

Inverse Agonists

Answer 18

• Postsynaptic: Binds to receptors but induces opposite effect

Question 19

Presynaptic Agonist: Parkinson’s Disease (L-Dopa)

Answer 19

• Parkinson’s Disease- reduced dopamine levels
  - Medication: L-Dopa (dopamine precursor)
  - Molecule that the brain can use to make more dopamine
  - Can’t provide dopamine directly because it cannot pass the blood-brain barrier

Question 19

Presynaptic Agonist: Cocaine

Answer 19

• Inhibits reuptake of dopamine by blocking dopamine transporter
• Leaves more dopamine in the synaptic cleft causing it to bind to receptors more frequently than normal

Question 20

Presynaptic Agonist: Amphetamine

Answer 20

• Blocks and reverses dopamine transporter
• Increases levels of dopamine and norepinephrine
• Stimulation, euphoria, wakefulness, improved cognitive control
• Treatment of ADHD, narcolepsy, depression; athletic performance enhancer
• Adderall: Prescribed combination of amphetamine and dextroamphetamine

Question 21

Presynaptic Agonist: Selective Serotonin Reuptake Inhibitors (SSRIs)

Answer 21

• Blocks reuptake of serotonin
• Commonly prescribed antidepressant (prozac)

Question 22

Postsynaptic Agonist: Morhpine and Heroin

Answer 22

• Activate post-synaptic opioid receptors
• Euphoric, pain relief
• Mimics endorphins and enkephalins

Question 22

Postsynaptic Agonist: Synthetic Opiods; Fentanil and Carfentanil

Answer 22

• Fentinal 100x more potent than morphine
• Carfentanil is 100x more potent than fentinal
• Pain relief, tranquilizer darts
• Overdose inhibits brainstem breathing circuits

Question 23

Postsynaptic Agonist: Benzodiazepines

Answer 23

- Xanax, Valium - Sedative, hypnotic, anxiolytic, anti-epileptic, muscle relaxant - Binds to GABA receptors and facilitates GABA effects - Both it and GABA bind to receptors, and more Cl flows through

Question 24

Postsynaptic Antagonist: Antipsychotics

Answer 24

- Drugs for schizophrenia (pimazide, haloperidol) - Blocks D2 dopamine receptors - Prevent dopamine from activating - Atypical antipsychotics block serotonin as well as dopamine receptors

Question 25

How do drugs reach the synapse?

Answer 25

- The drug goes into the blood stream, then into the brain through the blood-brain barrier - Drug gets to the blood stream in a few ways - Oral ingestion (digestive system can decompose the drug, but it is easier) - Injection - Inhalation (short route to brain)

Question 26

Receptor Down-Regulation

Answer 26

- When there is a lot of a neurotransmitter/activator, the neuron reduces the amount of receptors to keep a baseline level of activation - You need more of the drug to get the same effect, which closes more receptors and so on - For something like chocolate, when you eat too much you may not enjoy it as much for this reason - Can cause withdrawal (under-activation)

Question 27

Neural Sensitization

Answer 27

- Hyper-responsive to drug - Dopamine sensitization and addiction (wanting vs. liking)

Question 28

Neurotoxicity

Answer 28

- Repeated exposure to a drug (often in large amounts) can kill cells - Amphetamine can kill dopamine neurons, but is toxic at 10x the street dose