Brain & Behavior: Clinical Neurochemistry

Front 1

In general, how do "fast" NTs work? slow?

what are examples of fast?

Back 1

Fast neurotransmitters include GABA and glutamate and bind directly on ion-gated channels

Slow neurotransmitters include the monoamines and work through G proteins and second messengers

Front 2

What are the monoamines?

Back 2

(NTs) slower
Dopamine
Norepinephrine
Serotonin

Front 3

What are the non monoamines?

Back 3

Acetylcholine
GABA
Glutamate

Front 4

What are the catecholamines?

Back 4

Dopamine
Norepi and Epi

Front 5

where is the substantia nigra? what is it's function?

Back 5

The substantia nigra is a brain structure located in the mesencephalon (midbrain) that plays an important role in reward, addiction, and movement.

"black substance"

Front 6

what makes up the striatum?

Back 6

caudate and putamen

Front 7

* What are the main cell bodies producing dopamine?

hint: long, intermediate and short

Back 7

Long tracts: Substantia nigra --> primarily to striatum

Ventral tegmental area --> striatum plus the mesolimbic and mesocortical systems

*most important to behavior (motor and schizophrenia)

Intermediate:
Hypothalamic --> pituitary (DA inhibits prolactin)

Short:
Olfactory
Retina

Front 8

What is the RL step in DA synthesis?

Back 8

action of tyrosine hydroxylase

(converts Tyrosine to DOPA)

Front 9

Can administered dopamine get into the brain?

Back 9

NO! blood brain barrier

so, L-DOPA given, later converted to dopamine

Front 10

* What is the main termination of monoamines (dopamine)?

Back 10

re-uptake

Front 11

What do MAO-B and COMT do?

Back 11

enzymes that degrade dopamine in the synapse

Front 12

What are the common features of monoaminergic receptors?

Back 12

7 membrane spanning regions

intracellular carboxy tail, extracellular amino region

highly conserved (small variations)

carry out function through g-proteins

Front 13

* What is the most common dopamine receptor and what is it's effect?

Back 13

D1 (monoaminergic)

stimulation of adenylate cyclase and increased production of cyclic AMP

Front 14

* Where are the D1 receptors found?

Back 14

striatum

but also abundantly in cortical and limbic regions

Front 15

how do D2 receptors differ from D1?

Back 15

inhibit adenylate cyclase

also found in striatum

Front 16

where are D3, D4 and D5 receptors primarily found?

Back 16

cortical and limbic regions

Front 17

What are the general functions of dopamine? serotonin?

Back 17

dopamine:
motor activity (parkinson's) as well as cognition (schizophrenia)
-also implicated in abuse/reward pathway

serotonin: regulation of mood and sleep
- involved in psychosis and implicated in pain and nausea

Front 18

* What are neuroleptics? how are they classified? and give an example of each.

Back 18

dopaminergic drugs

classified as typical (strong blockage of D2) and atypical (weak blockage of D1 and D2)

Haloperidol - typical, antipsychotic, can cause parkinson's

Clozapine - atypical antipsychotic

Front 19

* how does cocaine "work"?

Back 19

by blocking the reuptake of dopamine --> euphoria

Front 20

What are the effects of too much dopamine? too little?

Back 20

euphoria, confusion, psychosis

Parkinsonism

Front 21

what is the effect of amphetamine and amantadine on DA?

Back 21

promote presynaptic release

Front 22

* What are the two main molecules that degrade dopamine? what does it become?

Back 22

monoamine oxidase (MAOb) and catechol-O-methyltransferase (COMT) --> DOPAC and HVA

Front 23

What is the idopathic cause of Parkinson's?

Back 23

loss of dopaminergic neurons in substantia nigra

Front 24

What is the common MAOb inhibitor? (limits degradation of dopamine)

Back 24

deprenyl

Front 25

What happens to dopamine release and postsynaptic receptors in chronic cocaine use and withdrawal?

Back 25

poor release and few receptors (dopamine shortage in synapse)

Front 26

* where are the cell bodies for NorEpi?

Back 26

locus ceruleus (in the dorsal pons)

Front 27

Reuptake is the main termination method of NorEpi, what is the other degradation pathway?

Back 27

COMT --> Normetanephrine + MAO --> VMA (3 methoxy 4 hydroxy-mandelic acid)

MAO --> MHPG (3 methoxy-4 hydroxy-phenylglycol)

Front 28

* How is Norepinephrine synthesized?

Back 28

From dopamine --> (via dopamine b-hydroxylase) --> norepi

Front 29

What are the pre-synaptic receptors of NorEpi? post-synaptic?

Back 29

a-2 & b-2

a-1 & b-1

Front 30

What are phenoxyebenzamine and phentolamine?

Back 30

a-1 blockers (norepi) used in the treatment of htn

Front 31

what is clonidine? yohimbine?

Back 31

a-2 presynaptic agonist --> decreases sympathetic tone, used to treat htn

a-2 antagonist --> increases sympathetic tone (may lead to sexual arousal, panic and anxiety)

Front 32

what is richly innervated by norandergenic neurons from the locus ceruleus, and may play a role in panic disorder and formation of emotional memories?

Back 32

amygdala

Front 33

* where are the cell bodies of serotonin?

Back 33

dorsal raphe nuclei (midbrain) and caudal raphe nuclei (pons and medulla)

Front 34

where do the serotonin cell bodies project to?

Back 34

diffusely. striatum, limbic system, cortex, cerebellum... & spinal cord (caudal raphe)

Front 35

* what is the RL step in serotonin synth?

Back 35

availability of tryptophan

Front 36

reuptake is the main termination mechanism for serotonin, what are the other metabolizers?

Back 36

MAO and 5-HIAA

Front 37

What is another name for serotonin?

Back 37

5-HT (5-hydroxytryptamine)

Front 38

What NT has an effect on Sleep induction, Mood, Pain/headache, Nausea, Anxiety, Extrapyramidal system, Pleasure, Vasomotor tone, Psychosis?

Back 38

SEROTONIN !!

Front 39

What does resperpine do?

Back 39

depletes vesicular stores of serotonin ... may exacerbate depression

Front 40

What drug promotes presynaptic release of 5HT?

Back 40

Fenfluramine

Front 41

* With serotonin what do the tricyclic drugs (SSRI) do? what is this treating?

Back 41

inhibit reuptake; antidepressants

decreases serotonin => depression

Front 42

** What causes serotonin syndrome? what are the symptoms?

Back 42

too much serotonin released

Mental: confusion, agitation, restless
Motor: clonus, rigidity, hyperreflexia
ANS: shivering, flushing, fever
GI: nausea, diahrrhea

Front 43

* Where are the cell bodies of ACh? and where do they have rich connections to?

Back 43

Septal Nuclei and NBM (nucleus basilis of Mynert)

hippocampus and amygdala

Front 44

What is ACh the main NT for? (2)

Back 44

neuromuscular and ANS

Front 45

* What NT does botulinum toxin affect? what does it do?

Back 45

ACh

inhibits release

Front 46

What are the two primary receptor types for ACh?

Back 46

nicotinic and muscarinic

recall: nictotinics are at the nm_junctions and in the ANS

Front 47

* What is the major inhibitory NT in the brain?

Back 47

GABA

Front 48

Where are the main cell bodies of GABA?

Back 48

ubiquitous throughout the brain

high conc. in the striatum, hypothalamus, spinal cord, colliculi, and medial temporal lobe

Front 49

* what to antibodies formed against nicotinic cholinergic receptors at the nm_juction cause?

Back 49

myasthenia gravis

Front 50

** what disease is associated with decreased ACh? what enzyme is usually implicated?

Back 50

Alzheimer's

Choline acetyltransferase (CAT)

Front 51

What is aricept? what diseases does it treat?

Back 51

Acetylcholinesterase inhibitors

dementia (incl. AD)

Front 52

* How is GABA synthesized?

Back 52

from glutamate --> (glutamic acid decarboxylase - GAD) --> GABA

Front 53

What happens when GABA binds a GABA receptor?

Back 53

Chloride channel opens --> HYPERpolarizing = no APs

Front 54

how do benzodiazepenes function?

Back 54

by binding to GABA recpetor: enhance GABA affinity and activity --> treat anxiety, seizures, muscle spasms

* same effects as barbituates and alcohol

Front 55

What is Depakote?

Back 55

anticonvulsant, modulates GABA

Front 56

* What is the most common excitatory NT in the CNS?

Back 56

Glutamate (an amino acid)

Front 57

How is the regulation of glutamate reuptake? (general)

Back 57

tightly regulated

Front 58

* What are the glutamate receptors and how do they function?

Back 58

Glutamate binds NMDA receptor: ion channel --> Ca2+ and Na+ influx

AMPA receptor activation removes Mg block

Glycine must also bind its receptor to allow Ca2+ and Na+ influx

Front 59

* Where in the "NT system" does PCP play a role? how?

Back 59

Glutamate (NMDA receptor antagonists) --> limit exitotoxic injury but can produce psychotic symptoms

Front 60

Explain Haloperidol*

Back 60

Haloperidol is a potent D2 blocker and typical antipsychotic. It is an effective antipsychotic but can cause Parkinsonism, tardive dyskinesia (TD) and cognitive slowing.

Front 61

Explain Clozapine*

Back 61

Clozapine is an atypical antipsychotic with weak antagonism at D1 and D2 receptors and blocks 5HT2 serotonin receptors. It may exert its antipsychotic effect by blocking D4 receptors, thereby sparing the striatum. Clozapine does not normally cause extrapyramidal symptoms, TD, or increased prolactin.