Brain substrates - Catecholamines Flashcards
What are catecholamines?
A group of biogenic amines that are derivatives of catechol and contain an amine group.
What common neurotransmitters are catecholamines?
Dopamine, adrenaline and noradrenaline.
How are catecholamines synthesised?
In a multi-step pathway (tyrosine, DOPA, dopamine, noradrenaline).
What enzymes are used to synthesise noradrenaline?
Tyrosine hydroxylase (TH), aromatic amino acid decarboxylase (AADC) and dopmaine beta-hydroxylase (DBH).
What enzymes are used to synthesise dopamine?
Tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC).
Which enzyme is the rate-limiting enzyme in the pathway to synthesise catecholamines?
Tyrosine hydroxylase (TH). It's slower and therefore determines the overall rate of catecholamine production.
What do high catecholamine levels do?
Inhibit TH production = negative feedback mechanism.
What enzyme does neuronal activity stimulate?
TH. Helpful during stress, for example - can accelerate production.
What does catecholamine depletion cause in rabbits?
Behavioural sedation, which is reversed by treatment with DOPA.
(As shown by injecting rabbits with reserpine).
What is the role of autoreceptors in neurons?
Self-regulation - inhibits catecholamine release by reducing the amount of Ca2+ that enters the terminal in response to an impulse.
What are the three ascending dopamine pathways?
Nigrostriatal, mesolimbic and mesocortical.
What exactly does reserpine do?
Blocks both VMAT1 and VMAT2, meaning that catecholamines are no longer protected from breakdown in the nerve terminal.
What does VMAT stand for?
Vesicular monoamine transporter.
What does catecholamine depletion cause in humans?
Depressive symptoms.
Which drugs cause a release of catecholamines independent of nerve cell firing?
Psychostimulants - amphetamine and methamphetamine.
What does catecholamine release in animals cause?
Behavioural activation - at low doses, increased locomotor activity, and at high doses stereotyped behaviours.
What does catecholamine release in humans cause?
Increased alertness, heightened energy, euphoria and insomnia.
What structures are involved in the nigrostriatial tract/pathway?
The substantia nigra (A9), the globus pallidus and the striatum/caudate-putamen.
In what condition is the nigrostriatal pathway damaged?
Parkinson’s disease - there is a striking loss of nerve cells in the substantia nigra.
What ascending dopamine pathway is associated in the control of movement?
The nigrostriatal pathway.
What structures are involved in the mesolimbic dopamine pathway?
The VTA and various structures of the limbic system (nucleus accumbens, septum, amygdala and hippocampus).
Which dopamine pathway is implicated in natural reward and drug abuse?
Mesolimbic pathway.
What is the role of the nucleus accumbens?
It’s sort of the reinforcement centre of the brain.
What structures are involved in the mesocortical dopamine pathway?
The VTA and the cerebral cortex - hippocampus, lateral septum and anterior olfactory nucleus.