Monoaminergic Transmission

Front 1

What are the 5 main monoamine neurotransmitters?

Back 1

1.Dopamine
2.Norepinephrine
3.Epinephrine
4.Serotonin
5.Histamine

Front 2

How are the catecholamines synthesized? which is the rate-limiting step?

Back 2

1.Tyrosine is hydroxylated to L-DOPA. This is the rate-limiting step
2.L-DOPA is decarboxylated to dopamine
3.Dopamine is hydroxylated to norepinephrine
4.Norepinephrine is methylated to epinephrine

Front 3

How is serotonin synthesized?

Back 3

1.Trytophan is hydroxylated to 5-HTP
2.5-HTP is decarboxylated to serotonin

Front 4

How is histamine synthesized?

Back 4

Histadine is decarboxylated to histamine.

Front 5

How are monoamines released from the pre-synaptic terminal?

Back 5

They are stored in secretory vesicles which are released in a Ca++ mediated fashion.

Front 6

Describe the monoamine receptors on the postsynaptic terminal. Are they inhibitory of excitatory?

Back 6

The receptors are metabotropic and coupled to a G-protein. The effects of binding may be excitatory or inhibitory depending on the specific receptor.

Front 7

How are monoamines removed from the synaptic cleft?

Back 7

*catecholamines may be degraded by CoMT
*they may be taken back up by the pre-synaptic terminal via DAT, NET, or SERT

Front 8

What happens to monoamines that are taken back up by the pre-synaptic terminal?

Back 8

*they may be degraded by MAO
*they may be reloaded into secretory vesicles by VMAT

Front 9

What are autoreceptors?

Back 9

They are receptors found on the pre-synaptic membrane that downregulate synthesis and release of neurotransmitter when activated.

Front 10

T/F:
Monoaminergic neurons are among the most important in the brain and make up a large proportion of the total cell population.

Back 10

False: monoaminergic neurons are very important, but they only make up a small fraction of the total number of neurons.

Front 11

Where does the nigrostriatal pathway originate from? Where does it project?

Back 11

*originates in the substantia nigra
*projects to the striatum (caudate and putamen)

Front 12

What effects are seen with loss of neurons in the nigrastriatal pathway?

Back 12

Parkinson's symptoms

Front 13

Where does the mesolimbic pathway originate from? Where does it project? What neurotransmitter is carried on this path?

Back 13

*originates at the midbrain tegmentum
*projects to the limbic system, especially the nucleus accumbens
*dopamine

Front 14

What is the function of the mesolimbic pathway?

Back 14

It is part of the "reward" circuit of the brain.

Front 15

Where does the mesocortical pathway originate from? Where does it project? What disease is said to involve malfunction in this pathway?

Back 15

*originates from the midbrain tegmentum
*projects to the cerebral cortex
*schizophrenia

Front 16

What are the three dopaminergic pathways in the brain?

Back 16

1.Nigrostriatal
2.Mesolimbic
3.Mesocortical

Front 17

Where does the noradrenergic pathway originate? Where does this path project?

Back 17

*locus coeruleus
*projects through the MFB to the rest of the cerebrum
*also projects to the cerebellum and spinal cord

Front 18

What is the function of the noradrenergic pathway?

Back 18

This pathway is thought to be involved in arousal, attention, and feeding.

Front 19

Which of the monoaminergic pathways pass through the MFB?

Back 19

*noradrenergic
*serotoninergic

Front 20

Where does the serotoninergic pathway originate from? Where does it project to?

Back 20

*originates at the raphe nuclei of the midbrain
*projects through the MFB to the cerebrum
*also projects to the spinal cord to interact with descending pain control pathways

Front 21

Where does the histamine pathway originate? What is the function of this pathway?

Back 21

*originates at the tuberomammillary nuclei of the hypothalamus
*involved in arousal and wakefulness

Front 22

What is the effect of inhibition of the H1 receptor? What drug is known to do this?

Back 22

*blocking this histamine receptor results in sedation
*benadryl

Front 23

T/F:
Tolerance is largely a psychological phenomenom.

Back 23

False: tolerance is a physiological adaptation.

Front 24

Which monoaminergic pathway has been implicated in substance abuse?

Back 24

The mesolimbic dopaminergic pathway - the "reward" circuit of the brain.

Front 25

What is the mode of action of cocaine and amphetamine?

Back 25

They block pre-synaptic uptake of dopamine and norepinephrine, thus prolonging the time these neurotransmitters are in the synaptic cleft.

Front 26

Why are MAO inhibitors seldom used for treatment of depression?

Back 26

They have serious side effects related to accumulation of tyramine, which is also broken down by MAO.

Front 27

What is the mode of action of the tricyclic antidepressants?

Back 27

By inhibiting DAT, NET, and SERT they block the re-uptake of these neurotransmitters.

Front 28

What is the mode of action of the SSRIs?

Back 28

By inhibiting the action of SERT, it blocks the reuptake of serotonin.

Front 29

What has been shown to be the most effective treatment for depression?

Back 29

ECT, with a success rate of 85%.

Front 30

How is lithium thought to work in the treatment of bipolar disorder?

Back 30

It is thought to inhibit second messenger pathways in the post-synaptic terminal.

Front 31

What are some "positive" symptoms of schizophrenia? What are some negative symptoms?

Back 31

*hallucinations (auditory and visual), delusions, paranoia, disorganized thought
*poverty of thought, emotion and motivation; catatonia

Front 32

What kinds of anatomical changes are seen in the brains of schizophrenia patients?

Back 32

Atrophy with widening of sulci and ventricular enlargement, with emphasis at the vermis, hippocampus, prefrontal cortex, and thalamus.

Front 33

What are two pieces of evidence that support the dopamine hypothesis of schizophrenia?

Back 33

1.Drugs which block dopaminergic transmission alleviate symptoms
2.Drugs that induce dopaminergic transmission cause psychosis

Front 34

What is the mode of the first generation neuroleptics? What side effects are associated with their use?

Back 34

They are specific D2 antagonists which prevent dopaminergic transmission. Side effects include Parkinsonism and problems of excessive movement: acute dystonia and tardive dyskinesia.

Front 35

Do second generation neuroleptics have a more or less specific mode action as compared to first generation drugs?

Back 35

Second generation neuroleptics have a broader mode of action and inhibit serotoninergic as well as dopaminergic transmission.

Front 36

What is the mode of action of the third generation neuroleptics?

Back 36

They are mixed agonist/antagonists of dopaminergic transmission that allow partial activation of receptors.

Front 37

What are two pieces of evidence AGAINST the dopamine hypothesis of schizophrenia?

Back 37

1.Antipsychotic drugs are not specific to dopaminergic transmission.
2.Psychosis may be produced by activation of other receptors.
3.Drugs block dopamine receptors right away, but symptoms may not disappear for days or weeks.