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Biogenic amines

- Regulate many brain functions but are also active in the peripheral
nervous system.
- Implicated in a large variety of functions (attention/homeostasis).
- Defects in biogenic amine functions are implicated in most
psychiatric disorders.

Serotonin and depression:

Depression= mental disorder characterized by persistent low-mood, low

self-esteem, loss of interest and pleasure.
- SSRI increase the extracellular level of the neurotransmitter
serotonin by limiting its reabsorption into the presynaptic cell,
increasing the level of serotonin in the synaptic cleft available to
bind to the postsynaptic receptor
- We dont how exactly serotonin is involved in depression
- Side-effects:
- Insomnia, weight loss, mania, tremor, nausea, cognitive
disorders, diarrhea.
- Serotonin is heavily involved in food regulation a lot of side-
effects affect the gastro-intestinal tract

Norepinephrine (noradrenaline)
- influences sleep wakefulness, attention and feeding behavior
- locus coeruleus

Epinephrine (adrenaline)
- medullary epinephrine neurons
- fight and flight behaviour
- autonomous nervous system (heart rate, dilatation, sweat, saliva)
- substantia nigra and ventral tegmental area
- Activation of certain dopamine receptors causes hyperactivity and
stereotyped behaviour.
- Reward, attention, motor behaviour
- Dopamine receptor antagonists can induce vomiting (Medulla).
- Dopamine receptor antagonists can elicit catalepsy (decreased
ability to initiate movement).
- Cocaine increases the amount of dopamine in the synaptic cleft
- 4 different pathways that dopamine is involved in
- Nigrostriatal pathway
- Substantia nigra to striatum.
- Involved in the production of movement.
- Tuberoinfundibular pathway
- Arcuate nucleus of the hypothalamus to the
pituitary gland.
- Influences secretion of hormones such as prolactin
(involved in lactation).
- Mesocortical pathway
- Ventral tegmentum to cerebral cortex (frontal
- Involved in motivation and emotional response.
- Thought to be associated with the negative
symptoms of schizophrenia including apathy,
listlessness and poverty of speech
- Mesolimbic pathway
- Ventral tegmentum to the limbic system via
nucleus accumbens, the amygdala and
hippocampus and to the medial prefrontal cortex.
- Associated with feelings of reward and desire.
- Implicated in addiction and depression, associated
with the negative symptoms of Schizophrenia such
as delusions, disordered thoughts and speech or
- Cocaine block the dopamine reuptake transporter
at the presynaptic neuron

you cant selectively target one pathway, you will

affect all of them

- Dopamine and Parkinsons: : rigor, bradykinesia (akinesia),

tremor and postural instability.
- The substantia nigra loses its dark shading due to the death of
neurons less expression of dopamine nigrostriatal
pathway affected movement impairments
- Treatment: L-Dopa because dopamine doesnt cross the blood-
brain barrier
- To use L-Dopa, you need to have those neurons, so it is
a good treatment in earlier stages of the disease, but
not in the later stages
- The basal ganglia: 2 pathways involved in movements
- Direct pathway and indirect
Unconventional neurotransmitters

- Not stored in synaptic vesicles.

- Not released from presynaptic terminals via exocytotic
mechanisms .
- Need not be released from presynaptic terminals at all.
- Often associated with retrograde signaling (from postsynaptic cells
back to presynaptic terminals).
- Endocannabinoids and Nitric oxide.
- Cannabinoid receptors are the molecular target of the 9
tetrahyrocannabinol (THC), the psychoactive component of
- CB1 receptors in the neocortex: effects on perception.
- CB1 receptors in the basal ganglia: effects on motor behaviour.
- CB1 receptors in the hippocampus: effects on short-term memory.
- CB1 receptors in the hypothalamus: effects on appetite.

How the nigrostriatal pathway (Parkinsonian symptoms) works:

Substantia nigra has a transient (temporarily) excitatory effect (excites)

on the caudate and the putamen which transiently inhibit the globus
pallidus. The globus pallidus tonicly (constantly) (inhibites) the ventral
area of the thalamus which transiently excites the frontal cortex.

In parkinsons: if the substantia nigra does not excite the caudate and
putamen (less inervation) less inervation/inhibition of globus pallidus
more inhibition of the thalamus decrease excitatory signal

What are the main biogenic amines, and what is special about
The main biogenic amines are serotonin, dopamine, epinephrine and
norepinephrine. They are found in the brain and also in the
peripheral nervous system and are involved in a large variety of
functions (attention/homeostasis). They are also linked to most
psychiatric disorders.

Describe the four dopaminergic pathways.

The mesocortical pathway goes from the ventral tegmentum to the
frontal lobes. Its main functions are linked with emotional and
intellectual operations (motivation and emotional response). It is
associated with schizophrenias symptoms such as apathy,
listlessness and poverty of speech.

The mesolimbic pathway goes from the ventral tegmentum to the

limbic system and the nucleus accumbens. It deals with reward and
desire. Main symptoms in schizophrenia are associated with
hallucinations, delusions and disordered cognitions. Cocaine blocks
the dopamine reuptake transporter at the presynaptic neuron.

The nigrostriatal pathway goes from the substantia nigra to the

striatum. It deals with movement.

The tuberinfundibular pathway goes from the hypothalamus to the

pituitary gland and it is involved in the endocrine regulation.

Describe the Mesolimbic pathways involvement in drug abuse and

The use of cocaine block the reuptake of dopamine at the synaptic
cleft, leaving more neurotransmitter for the postsynaptic neurons.
By consuming more, the receptors for dopamine might start getting
destroyed which makes the user crave for more.

Why do antipsychotic drugs have many side effects?

Antipsychotic drugs have many side effects because they cannot
affect only the neural pathway that they are destined to, but also
influence the other pathways.

What is Parkinsons disease and how are the basal ganglia involved?
Parkinsons disease is a disease in which movement is affected
because the neurons in the substantia nigra die. As the substantia
nigra cannot inervate the nigrostriatal pathway anymore, the frontal
cortex is less excited which leads to less movement.

What are unconventional Neurotransmitters?

Unconventional neurotransmitters are neurotransmitters that
are not stores in vesicles and do not need to be released through
exocytosis. They are often associated with retrograde signalling.
Endocannabinoids are an example of unconventional