dopamine

roles of dopamine

catecholamine neurotransmitter that:

• controls movement

• emotional response

• controls pleasure and pain

how is dopamine synthesised

• in presynaptic terminals of dopaminergic neurones

• made from amino acid tyrosine

• stored in large dense core vesicles

how is dopamine released

by vesicle exocytosis

where does released dopamine bind 

binds to dopamine receptors and produces excitatory or inhibitory postsynaptic effects depending on type of postsynaptic receptor

how is dopamine removed from the synaptic cleft

by dopamine transporters and it is degraded by enzyme monamine oxidase 

dopamine receptors are G protein coupled receptors. what are the 2 main classes

• D1-like dopamine receptors (D1, D5)

• D2-like dopamine receptors (D2, D3, D4)

what do D1-like dopamine receptors activate

activates G_s heterotromeric G-proteins

what happens when dopamine binds to D1-like receptor

α-subunit of the Gs protein dissociates from the βγ subunits

what enzyme does α-subunit of Gs protein stimulate

adenylyl cyclase

what is the effect of adenylyl cyclase activation

increases cAMP levels inside postsynaptic neurone

what does cAMP activate in D1 receptor signaling

protein kinase A (PKA)

how does activation of PKA affect neuronal excitability

PKA phosphorylates and stimulates voltage-gated ion channels, leading to increased excitability (EXCITATION) of the postsynaptic neuron

which G-protein class do D2-like dopamine receptors activate

Gi/o heterotrimeric G-proteins

what happens when dopamine binds to D2-like receptor

α-subunit of the Gi/o protein dissociates from the βγ subunits

what enzyme does α-subunit of Gi/o inhibit

adenylyl cyclase

what is the effect of adenylyl cyclase inhibition

reduces cAMP production leading to decreased activity of cAMP dependent pathways

how does inhibition affect neuronal excitability

causes inhibition of voltage-gated channels producing an overall inhibitory effect on postsynaptic neurone

how is dopamine action terminated at synapse

by reuptake of dopamine into presynaptic neurone via dopamine transporters (DAT)

true or false: process of dopamine reuptake is an energy-dependent process

true

which enzyme provides energy for dopamine reuptake

sodium/potassium ATPase which creates ion gradient that drives transporter function

how does dopamine transporter DAT move dopamine into the neurone

uses the Na⁺ and Cl⁻ ion gradient to co-transport dopamine from the synaptic cleft into the presynaptic terminal

what is the role of K⁺ ions in the dopamine transport cycle

K⁺ ions bind to the transporter, allowing it to reset to its outward-facing position after dopamine transport

why is K+ release back into synaptic cleft important

it restores ionic gradient across presynaptic membrane which enables another transport cycle

why is dopamine reuptake crucial for brain function

terminates synaptic signaling, prevents overstimulation and allows recycling of dopamine for future neurotransmission

what are the 3 main sources of dopamine in brain

1) ventral tegmental area

2) substantia nigra 

3) arcuate nucleus of hypothalamus

where are neurones of mesolimbic dopamine pathway located

in ventral tegmental area of midbrain

where do ventral tegmental area neurones of mesolimbic pathway project to 

limbic areas especially in nucleus accumbens

what is main function of mesolimbic dopamine pathway

regulates mood, motivation and reward processing

what happens when dopamine release is increased in the mesolimbic pathwa

can produce positive psychotic symptoms (e.g., hallucinations, delusions) and lead to aggressive or hostile behaviour

which mental health condition is associated with overactivity of the mesolimbic pathway

Schizophrenia (positive symptoms)

where do neurons from the VTA project in the mesocortical pathway

to prefrontal cortex

what does the mesocortical dopamine pathway regulate

• attention

• working memory

• executive functions

what symptoms are linked to reduced dopamine activity in the mesocortical pathway

• cognitive impairment

• apathy 

• negative symptoms of schizophrenia

where are the neurons of the nigrostriatal dopamine pathway located

in the Substantia Nigra of the midbrain

where do nigrostriatal neurons project to

the Striatum of the Basal Ganglia

what is the main function of the nigrostriatal dopamine pathway

regulation of movement and motor control

what are the effects of dopamine deficiency in nigrostriatal pathway

• rigidity

• akinesia

• bradykinesia

• tremor

what disease is caused by degeneration of nigrostriatal dopamine neurons

Parkison’s disease

what symptoms result from hyperactivity of nigrostriatal pathway

• chorea 

• dyskinesias

• tics

where are the neurons of the tuberoinfundibular dopamine pathway located

in the Arcuate Nucleus of the Hypothalamus

where is dopamine released in the tuberoinfundibular pathway

into the portal blood system connecting the hypothalamus and the anterior pituitary

what is the main target of dopamine in the tuberoinfundibular pathway

Prolactin-secreting cells (lactotrophs) in the anterior pituitary

what is the effect of dopamine on prolactin secretion

it inhibits prolactin release

what happens when dopamine activity in tuberoinfundibular pathway is reduced

Prolactin levels rise, leading to hyperprolactinaemia (which can cause galactorrhea and menstrual disturbances)

what are dopamine receptor agonists or mimetics

drugs that increase dopamine activity by stimulating dopamine receptors directly or indirectly

examples of drugs that increase dopamine availability by inhibiting dopamine reuptake

amphetamine and cocaine

what is the mechanism of action of amphetamine

reverses dopamine transporter (DAT) function, increasing dopamine release into the synaptic cleft and blocking reuptake

what is mechanism of action of cocaine

blocks dopamine reuptake by inhibiting the dopamine transporter (DAT), causing dopamine accumulation in the synaptic cleft

what example of dopamine precursor is used therapeutically

L-DOPA (levodopa)

what is L-DOPA used to treat

Parkinson’s disease, to restore dopamine levels in the nigrostriatal pathway

what are dopamine receptor antagonists (D2 antagonsits)

anti-schizophrenic or anti-psychotic drugs