Overview of Neurotransmitters Psych 223

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Overview of NeurotransmittersPsych 223

• February 23rd 2005

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Lecture Outline

• Some myths
• Some facts
• Categories of neurotransmitters
• Acetycholine
• Biogenic amines
• Amino acids
• Peptides

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Some Myths About Neurotransmitters

• One neuron, one neurotransmitter?
• The classic notion of a neuron held that there
  was one transmitter for every neuron. So along
  with other aspects of a neuron's phenotype, its
  size, shape, location, synaptic connectivity, was
  its neuropharmacology. A neuron was designated
  as serotonergic, cholinergic etc. However, this
  notion has been discarded.

Classic
Revised
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Some Myths About Neurotransmitters

• One neurotransmitter one receptor?
• Each neurotransmitter system contains several
  receptor subtypes.
• Each subtype binds the neurotransmitter with high
  affinity, but intrinsic activity may vary.
• Some subtypes may be predominately presynaptic
  while others are postsynaptic.
• Subtypes may be linked to different effecter
  systems.
• Drugs are often selective for one subtype.

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Some Myths About Neurotransmitters

• One neurotransmitter one receptor?
• Each neurotransmitter system contains several
  receptor subtypes.
• Each subtype binds the neurotransmitter with high
  affinity, but intrinsic activity may vary.
• Some subtypes may be predominately presynaptic
  while others are postsynaptic.
• Subtypes may be linked to different effecter
  systems.
• Drugs are often selective for one subtype.

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Some Myths About Neurotransmitters

• One neurotransmitter one receptor?
• Each neurotransmitter system contains several
  receptor subtypes.
• Each subtype binds the neurotransmitter with high
  affinity, but intrinsic activity may vary.
• Some subtypes may be predominately presynaptic
  while others are postsynaptic.
• Subtypes may be linked to different effecter
  systems.
• Drugs are often selective for one subtype.

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Some Myths About Neurotransmitters

• One neurotransmitter one receptor?
• Each neurotransmitter system contains several
  receptor subtypes.
• Each subtype binds the neurotransmitter with high
  affinity, but intrinsic activity may vary.
• Some subtypes may be predominately presynaptic
  while others are postsynaptic.
• Subtypes may be linked to different effecter
  systems.
• Drugs are often selective for one subtype.

Na
Adenylyl cyclase
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Some Myths About Neurotransmitters

• A digression on Adenylyl Cyclase..

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Some Myths About Neurotransmitters

• One neurotransmitter one receptor?
• Each neurotransmitter system contains several
  receptor subtypes.
• Each subtype binds the neurotransmitter with high
  affinity, but intrinsic activity may vary.
• Some subtypes may be predominately presynaptic
  while others are postsynaptic.
• Subtypes may be linked to different effecter
  systems.
• Drugs are often selective for one subtype.

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Some Myths About Neurotransmitters

• One neurotransmitter one receptor - 5-HT

Subtype Effector 5-HT1A Metabatropic (?
adenylyl cyclase) 5-HT1B 5-HT1D 5-HT1E
5-HT1F 5-HT2A Metabatropic (?
PLC) 5-HT2B 5-HT2C 5-HT3 Ionotropic 5-
HT4 Metabatropic (? adenylyl cyclase) 5-HT5A
Metabatropic (? adenylyl cyclase) 5-HT5B 5-HT
6 Metabatropic (? adenylyl cyclase) 5-HT7
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Some Myths About Neurotransmitters

• One neurotransmitter one behavior?
• Behaviors are mediated by an extraordinarily
  complex circuit of neurons. Even though we will
  discuss very complex behaviors in the context of
  a single neurotransmitter system. It is not the
  case that a single behavior is mediated by one
  neurotransmitter and it is not the case that one
  neurotransmitter mediates one and only one
  behavior.

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Some Facts About Neurotransmitters

• Localization
• The different types of neurotransmitters are
  distributed throughout the brain. However,
  certain nuclei are rich in specific
  neurotransmitters and are commonly associated
  with that neurotransmitter. For example,
  serotonin is abundant in the raphe nuclei, and
  the raphe provides much of the sertononergic
  enervation of the forebrain.

Serotonin pathways in the brain
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Some Facts About Neurotransmitters

• Localization

Dopamine pathways in the brain
Norepinephrine pathways in the brain
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Some Facts About Neurotransmitters

• Structure-Function
• There is a structure-function relationship in the
  brain where certain structures are critical for
  certain behaviors. For example, occipital cortex
  is responsible for vision and cerebellum is
  responsible for motor coordination. To the
  extent that neurotransmitters occur in higher
  concentrations in a given area, it would appear
  that those neurotransmitters are responsible for
  that behavior. At one level neurotransmitters are
  responsible for a given behavior, but function is
  the result of the connectivity of nuclei not the
  neurotransmitter.

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Some Facts About Neurotransmitters

• Criteria for a neurotransmitter
• Found in the pre-synaptic neuron
• Enzymes for synthesis are found in the
  pre-synaptic neuron
• There is a mechanism for terminating its action
• Direct application to the post-synaptic neuron
  induces the same effect as natural release
• When the pre-synaptic neuron is stimulated, the
  synapse should contain the transmitter
• Drugs that interfere with synthesis should block
  the effect of pre-synaptic stimulation
• Drugs that interfere with its post-synaptic
  effect should block the effect of pre-synaptic
  stimulation
• Drugs that interfere with metabolism should
  prolong the effect of pre-synaptic stimulation

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Neurotransmitters

• Cholinergics
• Acetycholine
• Choline
• Catacholamines
• Norepeineprine
• Dopamine
• Indoleamines
• Serotonin
• Melatonin
• Amino Acids
• Glutamate
• GABA
• Glycine
• Histamine

• Peptides
• Enkephalins
• b-Endorphin
• Vassopressin
• CRH
• Oxytocin
• VIP
• Somatostatin
• TRH
• ACTH
• (see Table 6.1 in F, M Q)

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Neurotransmitters

• Cholinergics
• Acetycholine (Ach)
• Movement, arousal, ageing, memory
• Notable parathion, sarin, atropine, nicotine,
  curare
• Catacholamines
• Norepineprine (NE)
• Mood, arousal, eating, memory
• Notable clonidine, albutorol (ventolin),
  propranalol
• Dopamine (DA)
• Schizophrenia, drug abuse, motivation, motor
  movement
• Notable cocaine, haloperidol
• Indoleamines
• Serotonin (5-HT)
• Mood, appetite, aggression, , OCD, sleep
• Notable prozac, LSD, fenfluramine

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Neurotransmitters

• Amino Acids
• Glutamate
• Ubiquitous learning and memory, cell death
• Notable MSG
• GABA
• Ubiquitous epilepsy, alcohol
• Notable valium

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Distribution in the Brain

• Acetyocholine 5
• Norepinephrine 2-3
• Dopamine 5
• Serotonin 2-3
• Amino Acids 60
• Peptides 15