Chemical Transmission in CNS

Question 1

Which Neurotransmitters + receptors are involved in the sympathetic, parasympathetic, and somatic nervous systems?

Answer 1

Sympathetic:

• Noradrenaline (norepinephrine) on Alpha and Beta adrenoreceptors
• alpha-1 receptors cause release of intracellular calcium (via Phospholipase C), and stimulation of alpha-2 receptors lowers the activity of adenylate cyclase.
• Beta receptors stimulate adenylate cyclase resulting in increased intracellular levels of cyclic AMP;

Parasympathetic
-acetylcholine on muscarinic receptors

Somatic
-acetylcholine on nicotinic receptors

Question 2

How is noradrenaline degraded in CNS synaptic junction compared to ACh?

Answer 2

ACh is removed via reuptake channels in pre-synaptic membrane.

Noradrenaline is metabolized in CNS synaptic space. Different from PNS where noradrenaline is mainly removed via reuptake.

Question 3

What are the important enzymes metabolizing noradrenaline in the CNS?

Answer 3

MOA (pre + post synaptic) and COMT (post synaptic)

Question 4

Describe the central effects of drugs that interfere with peripheral transmitters?

Answer 4

Cocaine inhibits noradrenaline reuptake. Thus, only has chance to bind with extraneuronal receptors that are low affinity. Excludes the neuronal receptors that are high affinity.
Noradrenaline is associated with stimulant effects, mood, appetitie, cardiovascular.

Amphetamine displaces noradrenaline from storage vesicles.

Question 5

What are the steps of catecholamine (adrenaline/noradrenaline) biosynethsis from extracellular to intracellular partitions?

Answer 5

Tyrosine enters cell through its channels—>Tyrosine hydroxylase changes Tyrosine to L-DOPA—->DOPA decarboxylase changes L-DOPA to Dopamine–>Dopamine enters an intercellular vesicle through channel–> Dopamine Beta Hydroxylase changes Dopamine to Noradrenaline–> Noradrenaline changes to Adrenaline by PENMT enzyme.

Summary
Tyrosine–>L-DOPA–>[Dopamine–>Noradrenaline–>Adrenaline]

Question 6

Describe the CNS pathways that Dopamine effects?

Answer 6

1. Movement
   - ex with Parkinson’s where there is a depletion of dopamine in the basal ganglia–>L-DOPA (precursor) is used as tx
2. Behaviour
   - ex. with Schizophrenia, changes in dopamine rich areas (frontal cortex, basal ganglia, temporal lobe)
3. Dependence
   - ex. Dopamine action in nucleus accumbens and ventral segmental area
4. Pituitary Function
   - ex. prolactin secretion

Question 7

Describe the selectivity of cocaine and the root of it’s addiction.

Answer 7

Blocks noradrenaline, dopamine, and serotonin reuptake. Also Blocks Na+ channels (lead for local anaesthesia).

Dopamine effect is linked to dependancy.

Noradrenaline/serotonin effect is lead for anti-depressant drugs.

Question 8

Describe the basic extrapyramidal motor system with localization of neurotransmitters.

Answer 8

Within the Substantia Nigra, the Pars Compacta signals with DOPAMINE release to corpus striatum. Interneuron within the corpus striatum signals with ACh to an exiting neuron. Exiting neuron signals with GABA to pars reticulata (substantia nigra).

Pars reticulata signals to thalamus. Thalamus signals with GLUTAMATE to motor cortex.

Question 9

Given its function, what diseases would be expect to occur with damage to/deregulation of the basal ganglia?

Answer 9

Disorders of behaviour control (ex. tourettes, OCD, dystonia),

psychostimulant addiction (cocaine, amphetamine, nicotine),

and movement disorders (Parkinson’s disease, degeneration of dopamine producing cells in substantia nigra pars compacta; and Huntington’s disease, striatum dysfunction).

Question 10

Glutamate is excitatory and GABA is inhibitory. Which neurotransmitters can be both? How is this possible?

Answer 10

Serotonin and dopamine.

Depending on the receptor they are binding.

Question 11

Describe how type of receptor and its location can influences the effect of a NT.

Answer 11

Ligand gated ion channels may be excitatory (nicotinic, Na+ driven depolarization) or inhibitory (GABA A, Cl- influx causing hyperpolarization).

G-protein couples receptors will cause activation of second messengers, modulation of an ion channel/enzyme activity.
(ex. Muscarinic, alpha/beta adrenoceptors).

Post-synaptic receptors (dendritic regions) may influence action potential generation/modulation.

Pre-synaptic receptors may regulate neurotransmitter release.

Question 12

Which receptors are involved more with neuronal function vs neuronal survival?

Answer 12

Ligand gated (milliseconds) and G-protein couples receptors (seconds) are primarily functional.

Tyrosine kinase (minutes) and cytoplasmic/nuclear (hours) receptors are primarily survival