Brain substrates - Catecholamines

Question 1

What are catecholamines?

Answer 1

A group of biogenic amines that are derivatives of catechol and contain an amine group.

Question 2

What common neurotransmitters are catecholamines?

Answer 2

Dopamine, adrenaline and noradrenaline.

Question 3

How are catecholamines synthesised?

Answer 3

In a multi-step pathway (tyrosine, DOPA, dopamine, noradrenaline).

Question 4

What enzymes are used to synthesise noradrenaline?

Answer 4

Tyrosine hydroxylase (TH), aromatic amino acid decarboxylase (AADC) and dopmaine beta-hydroxylase (DBH).

Question 5

What enzymes are used to synthesise dopamine?

Answer 5

Tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC).

Question 6

Which enzyme is the rate-limiting enzyme in the pathway to synthesise catecholamines?

Answer 6

Tyrosine hydroxylase (TH).
It's slower and therefore determines the overall rate of catecholamine production.

Question 7

What do high catecholamine levels do?

Answer 7

Inhibit TH production = negative feedback mechanism.

Question 8

What enzyme does neuronal activity stimulate?

Answer 8

TH. Helpful during stress, for example - can accelerate production.

Question 9

What does catecholamine depletion cause in rabbits?

Answer 9

Behavioural sedation, which is reversed by treatment with DOPA.
(As shown by injecting rabbits with reserpine).

Question 10

What is the role of autoreceptors in neurons?

Answer 10

Self-regulation - inhibits catecholamine release by reducing the amount of Ca2+ that enters the terminal in response to an impulse.

Question 11

What are the three ascending dopamine pathways?

Answer 11

Nigrostriatal, mesolimbic and mesocortical.

Question 12

What exactly does reserpine do?

Answer 12

Blocks both VMAT1 and VMAT2, meaning that catecholamines are no longer protected from breakdown in the nerve terminal.

Question 13

What does VMAT stand for?

Answer 13

Vesicular monoamine transporter.

Question 14

What does catecholamine depletion cause in humans?

Answer 14

Depressive symptoms.

Question 15

Which drugs cause a release of catecholamines independent of nerve cell firing?

Answer 15

Psychostimulants - amphetamine and methamphetamine.

Question 16

What does catecholamine release in animals cause?

Answer 16

Behavioural activation - at low doses, increased locomotor activity, and at high doses stereotyped behaviours.

Question 17

What does catecholamine release in humans cause?

Answer 17

Increased alertness, heightened energy, euphoria and insomnia.

Question 18

What structures are involved in the nigrostriatial tract/pathway?

Answer 18

The substantia nigra (A9), the globus pallidus and the striatum/caudate-putamen.

Question 19

In what condition is the nigrostriatal pathway damaged?

Answer 19

Parkinson’s disease - there is a striking loss of nerve cells in the substantia nigra.

Question 20

What ascending dopamine pathway is associated in the control of movement?

Answer 20

The nigrostriatal pathway.

Question 21

What structures are involved in the mesolimbic dopamine pathway?

Answer 21

The VTA and various structures of the limbic system (nucleus accumbens, septum, amygdala and hippocampus).

Question 22

Which dopamine pathway is implicated in natural reward and drug abuse?

Answer 22

Mesolimbic pathway.

Question 23

What is the role of the nucleus accumbens?

Answer 23

It’s sort of the reinforcement centre of the brain.

Question 24

What structures are involved in the mesocortical dopamine pathway?

Answer 24

The VTA and the cerebral cortex - hippocampus, lateral septum and anterior olfactory nucleus.

Question 25

In what condition is the mesocortical dopamine pathway implicated?

Answer 25

Schizophrenia.

Question 26

What does unilateral damage to the nigrostriatal pathway cause?

Answer 26

Degeneration of dopaminergic fibres in the striatum. Affects motor ability.

Question 27

What is the typical effect of administering a DA receptor antagonist?

Answer 27

Suppression of spontaneous exploratory and locomotor behaviour, at a higher level cataplexy.

Question 28

Define cataplexy.

Answer 28

A lack of spontaneous movement.

Question 29

What happens to rat pups when they’re injected with haloperidol?

Answer 29

They show cataplexy and do not change position even when uncomfortable. Similar to effect seen in severe catatonic schizophrenia.

Question 30

What does current theory state is the cause of Parkinson’s Disease?

Answer 30

Dopamine neuron damage and eventual death from oxyradical-induced oxidative stress.

Question 31

What does loss of dopaminergic innervation of the striatum correlate with?

Answer 31

Symptom severity in Parkinson’s (Fischmann et al., 1998).

Question 32

What, according to Giros et al (1996), is the most obvious characteristic of DA transporter knockout mice?

Answer 32

They are hyperactive - DA neurons can’t remove DA from the synaptic cleft so postsynaptic cells are exposed to excessive amounts.

Question 33

What did M.Xu et al (2000) find about D1 receptor knockout mice?

Answer 33

They are unaffected by psychostimulants (cocaine).

Question 34

What did Stine et al (2002) find?

Answer 34

That when opioid-dependent patients were infused with either yohimbine (NA a2 receptor antagonist) or a saline solution, yohimbine caused a rapid increase in experimenter-rated withdrawal symptoms over the next hour.

Question 35

Where does the ascending noradrenergic system originate?

Answer 35

In the locus coeruleus (A6), a small area of the pons. It contains a dense collection of noradrenergic neurons which provide nearly all the NA in the cortex, limbic system, thalamus and hypothalamus.

Question 36

Where does the locus coeruleus project to?

Answer 36

Almost all regions of the forebrain as well as the cerebellum and spinal cord. It’s the only NA pathway.

Question 37

What are the two families of adrenergic receptors?

Answer 37

Alpha and beta.

Question 38

What did Berridge et al (2003) find about the effect of noradrenergic agonists?

Answer 38

After either alpha or beta agonists (phenylephrine and isoproteronol) (or both - strongest effect), rats stayed awake longer.

Question 39

According to Aston-Jones (1985), what is the role of the locus coeruleus in vigilance?

Answer 39

LC firing is activated by arousing sensory stimuli and inhibited during maintenance behaviours such as sleeping, grooming and eating. Therefore it may be important in vigilance, i.e. attentiveness to important external stimuli.