LECTURE 1 (Brain Metabolism)

Question 1

What is Neurotransmission?

Answer 1

Process by which neurons communicate with one another using neurotransmitters (Synaptic transmission)

Question 2

Every neurotransmission consists of which parts?

Answer 2

• Presynaptic membrane
• Synaptic cleft
• Postsynaptic membrane

Question 3

Describe Norepinephrine (NE)

Answer 3

• Stress/panic hormone
• Increased levels = ANXIETY
• Decreased levels = DEPRESSION
• Tricarboxylic acid
• Some antidepressants increase Norepinephrine reuptake inhibitors
• Activated in Opiate withdrawal

Question 4

What is the main source of Norepinephrine in the brain and where is it located?

Answer 4

Locus Coeruleus

LOCATION: Posterior pons, near 4th ventricle

Question 5

Describe Dopamine (DA)

Answer 5

• Synthesised in Ventral tegmentum and Substantia nigra (midbrain)
• Increased levels = Schizophrenia -> meds: DA antagonists (HALOPERIDOL)
• Decreased levels = Parkinson’s disease & Depression -> meds: DA antagonists (LEVODOPA/CARBIDOPA)

Question 6

Describe GABA

Answer 6

• Largely inhibitory
• Synthesised in Nucleus Accumbens (NA activated in drug addiction and fear)
• Important for pleasure/reward
• GABA antagonists used in anaesthesia, schizophrenia, seizures
• Decreased levels: ANXIETY & HUNTINGTON’S DISEASE

Question 7

What are the GABA Receptor subtypes?

Answer 7

• GABAa & GABAb in Brain
• GABAc in Retina

Question 8

______________ act on GABAa and stimulate Cl- influx

Answer 8

Benzodiazepines

Question 9

What are some GABAa antagonists?

Answer 9

• Alcohol
• Zolpidem
• Barbiturates

Question 10

Explain how GABA has an inhibitory effect

Answer 10

GABA receptor activation -> Cl- influx into cell -> Hyperpolarisation (more negatively charged) -> Harder for neuron to depolarise and conduct action potential

Question 11

Describe GABA metabolism

Answer 11

• Synthesised by GLUTAMATE DECARBOXYLASE from GLUTAMATE
• Broken down by GABA TRANSAMINASE into breakdown products
• Both enzymes need B6 cofactor

Question 12

What does B6 deficiency lead to?

Answer 12

Seizures

Explanation: decreased activity of GABA-producing enzymes

Question 13

Describe Serotonin

Answer 13

• Synthesised in Raphe Nucleus (pons)
• Decreased levels: Anxiety & Depression

[many antidepressants work by raising serotonin levels]

Question 14

What are examples of Antidepressants?

Answer 14

• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Monoamine Oxidase Inhibitors (MAOi)
• Serotonin & Norepinephrine Reuptake Inhibitors (SNRIs)

Question 15

What is Serotonin Syndrome?

Answer 15

Serotonin syndrome is a potentially life-threatening condition precipitated by the use of drugs that increase Serotonin

SYMPTOMS:
- Mental state changes (anxiety, delirium, restlessness disorientation)
- Autonomic hyperactivity (diaphoresis [increased sweating], tachycardia, hyperthermia)
- Neuromuscular abnormalities (tremor, clonus [increased muscle contractions], hyperreflexia, bilateral Babinski sign)

TREATMENT:
- CYPROHEPTADINE (5-HT antagonist)

Question 16

Describe Acetylcholine

Answer 16

• Synthesised in basal nucleus of Meynert (forebrain)
• Increased levels = REM sleep
• Decreased levels = Alzheimer’s & Huntington’s disease

Question 17

Describe Phencyclidine (PCP)

Answer 17

Antagonist to NMDA receptor

MANIFESTATIONS:
- Violent behaviour
- Hallucinations
- Ataxia, Nystagmus (repetitive, uncontrolled movements)
- Hypertension, Tachycardia, Diaphoresis
- Can cause seizures, coma or death

Question 18

Describe Glutamate

Answer 18

• Major excitatory neurotransmitter
• Target receptor = N-methyl-D-aspartate (NMDA)
• Involved in pathogenesis of Huntington’s disease
• Neuronal death from GLUTAMATE TOXICITY

Question 19

How does Glutamate lead to cell death?

Answer 19

1) Glutamate binds NMDA receptor
2) Excessive Ca2+ influx
3) Cell death