02 Neurotransmitters

Neurotransmitters
1
Defining a Neurotransmitter
 Secreted factor from neurons
 Limited to a specific population
 Regulated synthesis, enzyme
 Produce a measurable effect
 Bind a specific, saturable receptor
 Release in response to stimulus from
axon terminal
 Storage in vesicles
 Degradation and/or re-uptake 2
TRANSPORT AND
UPTAKE INTO VESICLES
SYNTHESIS RELEASE
Life cycle of
neurotransmitters
DEGRADATION POST-SYNAPTIC
OR RE-UPTAKE RECEPTORS
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 Neurotransmitters and Neuromodulators
 Acetylcholine: Neuromuscular junction
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Copyright © 2004 Allyn and Bacon
Allyn & Bacon 2004 6
Functions of Ach in the CNS
• Basal Forebrain: arousal and attention
– Learning and memory
– Alzheimer Disease
• Parabrachial nucleus: REM sleep
– Continue to fire during REM
– # cells correlate with REM sleep
• Reward and Addiction (striatum?)
• Pain and other sensory input
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 Acetylcholine
 Botulinum toxin:
 An acetylcholine antagonist; prevents release by terminal
buttons.
 Black widow spider venom

 A poison produced by the black widow spider that
triggers the release of acetylcholine.
 Neostigmine:
 A drug that inhibits the activity of acetylcholinesterase.
 Hemicholinium:
 A drug that inhibits the uptake of choline.
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 Monoamines
 Catecholamines
 Dopamine (DA)
 Norepinephrine (NE)
 Epinephrine
 Indolamines
 Serotonin (5-HT)
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 Monoamines
 Dopamine:
 Produces both excitatory and inhibitory postsynaptic

potentials.
 Implicated in movement, attention, learning, reinforcing
effects of abused drugs.
 Synthesized from tyrosine that we obtain from our diet.
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Allyn & Bacon 2004 14 Bacon
Copyright © 2004 Allyn and
 Monoamines
Dopamine
 Nigrostriatal system:
 A system of neurons originating in the substantia nigra
and terminating in the neostriatum (caudate nucleus and
putamen of the basal ganglia); appears to play a role in
the control of movement.
 Parkinson’s Disease:
 A neurological disease characterized by tremors, rigidity of the
limbs, poor balance, and difficulty in initiating movements;
caused by degeneration of the nigrostriatal system; Parkinson’s
disease has been treated with L-DOPA.
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 Monoamines
Dopamine
 Mesolimbic system:
 A system of dopaminergic neurons originating in the
ventral tegmental area and terminating in the nucleus
accumbens, amygdala, and hippocampus; appears to
play a role in the reinforcing effects of drugs that are
commonly abused.
 Drug abuse/addiction
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 Monoamines
Dopamine
 Mesocortical system:
 A system of dopaminergic neurons originating in the
ventral tegmental area and terminating in the prefrontal
cortex; appears to influence formation of short-term
memories, planning, and preparing strategies for problem
solving.
 Schizophrenia
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 Monoamines: Dopamine
 MT: (synthesis blocker)
 A drug that blocks the activity of tyrosine hydroxylase
and thus interferes with the synthesis of the
catecholamines.
 Reserpine: (Vesicle blocker)

 A drug that interferes with the storage of monoamines in
synaptic vesicles by blocking the VMAT2 vesicle
transporter for DA, NE, and 5-HT.
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 Termination of Signaling:
 Monoamine oxidase (MAO)

 A class of enzymes that destroy the monoamines; dopamine,
norepinephrine, and serotonin.
 Deprenyl
 A drug that blocks the activity of MAO-B; acts as a dopamine
agonist. Also used to treat Parkinson’s disease.
 Dopamine Transporter (DAT)
 Reuptake of DA into pre-synaptic terminal
 DA may be oxidized and damage other proteins if not imported
into vesicles by the VMAT
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 Apomorphine: (acts as agonist)

 A drug that blocks dopamine autoreceptors at low doses;
at high doses binds postsynaptic receptors as well.
 Methylphenidate: (acts as agonist)

 A drug that inhibits the reuptake of dopamine; also
known as “Ritalin”; used to treat children with attention
deficit disorder.
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 Monoamines
Norepinephrine (NE)
 Norepinephrine is synonymous with noradrenaline.
 Found in neurons of the brain and the autonomic nervous

system.
 Almost every region of the brain receives input from

noradrenergic neurons.
 Implicated to play central role in vigilance or attentiveness to

events in the environment.
22
 Monoamines
Norepinephrine (NE)
 Locus coeruleus:
 A dark-colored group of noradreneric cell bodies located
in the pons near the rostral end of the floor of the fourth
ventricle.
 Many NE neurons release NE non-synaptically, from
axonal varicosities
 Greater diffusion, reach more targets
24
Firing Rate of LC neurons
25
•Fusaric acid:
A drug that inhibits the
activity of the enzyme
dopamine-ß-hydroxylase
and thus blocks the
production of
norepinephrine. Copyright © 2004 Allyn and Bacon
 Monoamines
Serotonin (5-HT)
 Serotonin:
 Serotonin is an indolamine neurotransmitter; also called
5-hydroxytryptamine (5-HT); thought to play a role in the
regulation of mood, the control of eating, sleep,
dreaming, and arousal; also thought to be involved in the
regulation of pain.
27
PCPA:
A drug that
inhibits the
activity of
tryptophan
hydroxylase and
thus interferes
with the
synthesis of 5-
HT.

 Monoamines
Serotonin (5-HT)
 M system:
 A system of serotonergic neurons that originates in the median
raphe nucleus; is a axonal fibers are thick and rounded and
appear to form conventional synapses with other neurons.
 D system:
 A system of serotonergic neurons that originates in the dorsal
raphe nucleus; its axonal fibers are thin, with spindle-shaped
varicosities that do not appear to form synapses with other
neurons.
30
 Monoamines
Serotonin (5-HT)
 5-HT Transporter:
 Energy dependent re-uptake of 5-HT back into the
pre-synaptic terminal.
 Fluoxetine (Prozac):
 A drug that inhibits the reuptake of 5-HT.
 Used as an anti-depressant, also to treat OCD and
anxiety.
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Serotonin Transporters
32
 Monoamines
Serotonin (5-HT)
 Fenfluramine:
 A drug that stimulates the release of 5-HT and prevents its
uptake; used as an appetite suppressant.
 LSD:
 Lysergic acid diethylamide
 This drug produces distortions of visual perceptions
(hallucinations).
 A drug that stimulates 5-HT2a receptors.
 MDMA (ecstasy):
 NE and 5-HT agonist: excitatory and hallucinogenic effects
 Causes transporters to run backward (extrude neurotransmitter
that is not secluded in vesicles)
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 Amino Acids
 The most common amino acid transmitters are:
 Glutamate
 Gamma-amino-butyric acid (GABA)
 Glycine
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 Amino Acids
 Glutamate
 Glutamate:
 An amino acid; the most important excitatory
neurotransmitter in the brain.
Synthesis:
ketoglutarate glutamate
TCA cycle
intermediate
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Glutamate Role in Learning

A balance of excitation and inhibition

 Amino Acids
 GABA:
 An amino acid; the most important inhibitory
neurotransmitter in the brain and spinal cord.
 Biosynthesis:
 Glutamate Glutamic acid
GABA
Decarboxylase (GAD)
 Allylglycine:
 A drug that inhibits the activity of GAD and thus blocks
the synthesis of GABA.
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 Amino Acids
 GABA
 Benzodiazepines:
 A category of anxiolytic drugs; an indirect agonist for the
GABAA receptor.
 A class of ligands in its own right: agonists, antagonists, and
inverse agonists exist for this site
 Anxiolytics (valium)
 Muscle relaxers
 Sleep aids (ambien)
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 Peptides
 Neurons of the central nervous system release a large

variety of peptides.
 A neuron manufactures both the polypeptides and the

enzymes that it needs to break them apart.
 Synthesis takes place in the soma and they are

delivered to the terminal buttons by axoplasmic
transport. Further processing occurs in vesicles.
 Most peptides appear to serve as neuromodulators,

some act as neurotransmitter.
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 Peptides: Opioids
 Endogenous opioid:
 A class of peptides secreted by the brain that act as
opiates; drugs that affect opioid receptors reduce pain.
“runner’s high”
 Three types of opiate receptors: 
 Naloxone:
 A drug that blocks opioid receptors.
 Given to reverse overdose of heroin.
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Neurotransmitters and Neuromodulators
Peptides: Opioids
Role of endogenous opioids
 Analgesia: Activation of opiate receptors by

endogenous or synthetic opiates causes
reduction in pain sensitivity.
 Inhibition of species typical behaviors such as

fleeing and hiding.
 Reward and reinforcement, both of species

specific behaviors (mating and maternal care)
and of drugs of abuse.
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 Lipids
 Cannabinoid:
 A lipid; an endogneous ligand for receptors that bind with
THC, the active ingredient in marijuana.
 Anandamide:
 Produced and released on demand, not stored in vesicles.
 Inhibit function of 5-HT receptors, prevent vomiting.

3
 THC can be used to control nausea and vomiting in patients

receiving chemotherapy and radiation.
 Very effective in children.
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 Nucleosides
 Adenosine:
 A nucleoside; a combination of ribose and adenine;
serves as a neuromodulator in the brain.
 Released by neurons and glia in response to low oxygen
or glucose, activity dependent release.
 Causes vasodilation, which helps restore nutrient balance.
 Generally inhibitory—build up of adenosine is a precursor

to sleep.
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Neurotransmitters and Neuromodulators
Nucleosides
Caffeine:
Blocks adenosine receptors

Dis-inhibition leads to excitement
Repeated administration causes tolerance,

but not addiction (not positively reinforced)
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 Soluble Gases
 Nitric oxide (NO):

 A gas produced by cells in the nervous system; used as a
means of communication between cells.
 Especially important for blood vessel dilation and some
aspects of learning and memory storage.
 Nitric oxide synthase:

 The enzyme responsible for production of nitric oxide.
Occurs in several cell-specific isoforms.
 nNOS, iNOS, eNOS
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02 Neurotransmitters

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02 Neurotransmitters

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Neurotransmitters

 Black widow spider venom

 Produces both excitatory and inhibitory postsynaptic

 Reserpine: (Vesicle blocker)

 Monoamine oxidase (MAO)

 Apomorphine: (acts as agonist)

 Methylphenidate: (acts as agonist)

 Norepinephrine is synonymous with noradrenaline.

 Found in neurons of the brain and the autonomic nervous

 Almost every region of the brain receives input from

 Implicated to play central role in vigilance or attentiveness to

Copyright © 2004 Allyn and Bacon

 The most common amino acid transmitters are:

 Gamma-amino-butyric acid (GABA)

Allyn & Bacon 2004 37

Allyn & Bacon 2004 38

 Neurons of the central nervous system release a large

 A neuron manufactures both the polypeptides and the

 Synthesis takes place in the soma and they are

 Most peptides appear to serve as neuromodulators,

 Three types of opiate receptors: 

Role of endogenous opioids

 Analgesia: Activation of opiate receptors by

 Inhibition of species typical behaviors such as

 Reward and reinforcement, both of species

 Inhibit function of 5-HT receptors, prevent vomiting.

 THC can be used to control nausea and vomiting in patients

 Generally inhibitory—build up of adenosine is a precursor

Blocks adenosine receptors

Repeated administration causes tolerance,

 Nitric oxide (NO):

 Nitric oxide synthase:

Allyn & Bacon 2004 51

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