Download 11 Chapter 2. Neurotransmitters and Receptors Chapter 2 Summary

Chapter 2. Neurotransmitters and Receptors
Chapter 2 Summary
Neurotransmitters are the biochemicals that carry information from one neuron to
another. When an action potential arrives at the terminal axonal membrane, a
neurotransmitter may be released into the synapse, where it can then diffuse
through the synaptic fluids and interact with the receptors on either the
presynaptic neuron or the postsynaptic neuron.
Many different types of neurotransmitters exist, each with its own functions and
neuroanatomical location. Dopamine, serotonin, and norepinephrine are common
neurotransmitters that appear to have important roles in psychopharmacology, as
many psychotropic drugs appear to interact with these neurotransmitters.
Neurotransmitters interact with protein with protein structures referred to as
receptors. Receptors are often located in the neuronal membrane and interact in a
lock-and-key fit with neurotransmitters. A given neurotransmitter may have
many different types of receptors that interact with only that neurotransmitter.
However, each of these receptors functions in a way unique from the other
receptors. For example, while serotonin has several different kinds of receptors,
each of these has its own physiological role. Most psychotropic drugs appear to
initiate their responses by interacting in some way with receptors, making
psychopharmacology, in many ways, the study of receptor physiology.
The interaction of a neurotransmitter with a psychoactive drug is merely the
beginning of a complicated biochemical chain of events that involves numerous
other events. All of these events appear to be involved in generating the final
behavioral responses. Furthermore, many of the adverse effects that so plague
psychopharmacology also appear to be mediated through receptors. The binding
of neurotransmitters to receptors, in some cases, results in the opening of ion
channels in the neuronal membrane, which results in a fast cellular response to the
neurotransmitter. In other cases, the binding of a neurotransmitter to its receptor
results in a complex chain of biochemical reactions involving numerous other
chemical entities called second messengers. Ultimately, these second messengers
are thought to lead to physiological or behavioral responses.
Chapter 2 Contents
Introduction
- importance of neurotransmitters and their receptors
- basic neurotransmitters, including acetylcholine, norepinephrine,
serotonin, dopamine, gamma amino butyric acid, glutamate
- post-receptor effects and second messengers.
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Neurotransmitters and Their Receptors
- receptors generally named after their neurotransmitters
- most psychotropic drugs initiate their effects through receptors
- storage of neurotransmitters in intraneuronal vesicles
- action potentials initiate release of neurotransmitters into synapse
- autoreceptors, neurotransmitter reuptake, reuptake antagonism,
monoamine oxidase, interaction with post-synaptic receptors
- ion channels and G proteins
- agonists and antagonists
- partial agonists
- specificity of neurotransmitters versus non-specificity of some
psychotropic drugs
- down regulation and up regulation
- serotonin: serotonin synthesis, dorsal raphe nuclei, serotonin 1a, 2, and
3 receptors
- norepinephrine: norepinephrine synthesis, alpha 1, alpha 2, beta 1, and
beta 2 adrenergic receptors, monoamine hypothesis, norepinephrine
and attention
- dopamine: dopamine synthesis, nigrostriatal pathway,
tuberoinfundibular pathway and prolactin, mesocorticolimbic pathway,
dopamine hypothesis of schizophrenia
- acetylcholine: synthesis, acetylcholine esterase, nicotinic and
muscarinic receptors, nucleus basalis of Meynert
- gamma amino butyric acid: major inhibitory neurotransmitter, GABAA
and GABA B receptor
- glutamate: excitatory neurotransmitter, glutamate transporter, kainate
receptors, metabotropic receptors, N-methyl-D-aspartate receptors,
glutamate hypothesis of schizophrenia
- opioid neuropeptides: enkephalins, endorphins, dynorphins,
endomorphins, mu, kappa, and delta receptors
- melatonin: pineal gland, suprachiasmatic nucleus
Summary
Suggested Readings
Siegel JM (2004): The neurotransmitters of sleep. Journal of Clinical Psychiatry
65 (supplement 16): 4-7
In reviewing the neurotransmitters and neurobiology of sleep, this article
provides a practical footing upon which to integrate the often abstract
research concerning neurotransmitters.
Murphy GM, Hollander SB, Rodrigues HE, Kremer C, Schatzberg AF (2004):
Effects of the serotonin transporter gene promoter polymorphism on mirtazapine
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and paroxetine efficacy and adverse events in geriatric major depression.
Archives of General Psychiatry 61: 1163-1169
The short 5HTTLPR allele of the serotonin transporter promotion region is
associated with a diminished response to antidepressants. This study
reviews the clinical relevance of the short 5HTTLPR allele in depressive
disorders and reports a differential antidepressant response to paroxetine
and mirtazapine in cases of geriatric depression associated with the short
5HTTLPR allele. The authors attribute the lessened response to
paroxetine in cases of 5HTTLPR to decreased tolerability to the drug
rather than to diminished efficacy.
Matrenza C, Hughes J-M, Kemp AH, Wesnes KA, Harrison BJ, Nathan PJ
(2004): Simultaneous depletion of serotonin and catecholamines in impairs
sustained attention in healthy female subjects without affecting learning and
memory. Journal of Psychopharmacology 18: 21-31
In this double-blind study of 20 female subjects, the authors found that
depletion of serotonin and catecholamines precursors resulted in a
sustained attention deficit, further implicating serotonin and catecholamine
function in cognition.
Berridge CW, Waterhouse BD (2003): The locus coeruleus-noradrenergic
system: modulation of behavioral state and state-dependent cognitive processes.
Brain Research Reviews: 42: 33-84
This review discusses the locus-coeruleus-noradrenergic system, including
its role in wakefulness and modulation of neuronal function. The authors
further discuss potential contributions of dysfunction in this system to
disorders of attention, sleep, and affect.
Bergstrom WH, Hakanson DO (1998): Melatonin: the dark force. Advances in
Pediatrics 45: 91-106
The authors provide a review on melatonin and its relationship to the
pineal gland. Various physiological effects of melatonin are reviewed also.
Multiple-Choice Questions
1. The cell bodies of norepinephrine-producing neurons are located in the
a. Dorsal raphe nuclei.
b. Septal nuclei.
c. The locus coeruleus.
d. The hypothalamus.
2. Which dopamine pathway is involved in the etiology of Parkinson’s disease?
a. Tuberoinfundibular.
b. Mesocortical
c. Mesolimbic.
d. Nigrostriatal.
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3. A major excitatory neurotransmitter in the brain is thought to be
a. Serotonin.
b. Norepinephrine.
c. Glutamate.
d. Gamma-amino-butyric acid.
4. The major inhibitory neurotransmitter in the brain is
a. Gamma-amino-butyric acid.
b. Serotonin.
c. Glutamate.
d. Dopamine.
5. Which type of receptor is coupled to chloride ion channels?
a. GABA.
b. Serotonin 1A.
c. Delta.
d. Mu.
6. Agonists
a. Inactivate their receptors.
b. Operate only on receptors linked to G proteins.
c. Activate their receptors.
d. Always increase the flow of sodium ions into a cell.
7. The binding of gamma amino butyric acid to GABAA receptors results in
a. An influx of chloride ions that tends to hyperpolarize the neuron.
b. An outflow of chloride ions that tends to depolarize the neuron.
c. An influx of sodium ions that tends to depolarize the neuron.
d. An outflow of sodium ions that tends to hyperpolarize the neuron.
8. Which is not a dopamine pathway?
a. Nigrostriatal.
b. Nucleus basalis of Meynert.
c. Tuberoinfundibular.
d. Mesocortical limbic.
9. Dopamine antagonism in the tuberoinfundibular pathway may result in
a. Elevations of acetylcholine in the nucleus basalis of Meynert.
b. Diminished acetylcholine in the nucleus basalis of Meynert.
c. Decreased prolactin.
d. Increased prolactin.
10. Metabotropic glutamate receptors
a. Control the release of prolactin.
b. Are linked to G proteins.
c. Increase chloride influx into the neuron.
d. Bind to endorphins.
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11. Mu, kappa, and delta receptors are directly coupled to
a. Chloride ion channels.
b. Voltage-gated sodium channels.
c. G proteins.
d. Metabotropic receptors.
12. The opiate receptor antagonist naloxone is used for the treatment of
a. Alcoholism.
b. Major depression.
c. Alzheimer’s dementia.
d. Elevated prolactin.
13. GABAB receptors are linked to
a. Chloride ion channels.
b. G proteins.
c. Voltage-gated sodium channels.
d. Monoamine oxidase.
14. Degeneration of the nigrostriatal pathway can result in
a. Parkinson’s disease.
b. Elevated prolactin levels.
c. Lowered output of acetylcholine in the nucleus basalis of Meynert.
d. Resolution of psychosis in people with schizophrenia.
15. Melatonin is produced in the
a. Dorsal raphe nuclei.
b. Locus coeruleus.
c. Suprachiasmatic nucleus.
d. Pineal gland.
16. Antagonists
a. Always result in an influx of chloride ions.
b. Prevent the receptors naturally occurring neurotransmitter from
binding to the neuron.
c. Activate the receptor to which they bind.
d. Only bind to inhibitory neurons.
17. Monoamine oxidase
a. Facilitates the repackaging of neurotransmitter into presynaptic
vesicles.
b. Metabolizes serotonin, dopamine, and norepinephrine.
c. Facilitates neurotransmitter binding to pre-synaptic receptors.
d. Facilitates neurotransmitter binding to post-synaptic receptors.
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18. A serotonin partial agonist would
a. Act as a relative serotonin antagonist under conditions of low synaptic
serotonin.
b. Act as a relative serotonin antagonist under conditions of high synaptic
serotonin.
c. Act as a relative agonist at dopamine receptors.
d. Act as a relative antagonist at dopamine receptors.
19. Putative roles for norepinephrine include all of the following but which one?
a. Mood regulation.
b. Attention.
c. Regulation of central nervous system prolactin concentrations.
d. A general regulation of overall brain tone.
20. The cell bodies for acetylcholine neurons are located in
a. The dorsal raphe nuclei.
b. The substantia nigra.
c. The locus coeruleus.
d. The nucleus basalis of Meynert.
Answers to Multiple-Choice Questions
1. c
2. d
3. c
4. a
5. a
6. c
7. a
8. b
9. d
10. b
11. c
12. a
13. b
14. a
15. d
16. b
17. b
18. b
19. c
20. d
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True-False Questions
1. Kainate receptors are linked to ion channels.
a. True.
b. False.
2. Synaptic concentrations of glutamate are regulated via glutamate transport
proteins.
a. True.
b. False.
3. Glutamate in the brain’s primary inhibitory neurotransmitter.
a. True.
b. False.
4. Gamma amino butyric acid is the brain’s primary inhibitory neurotransmitter.
a. True.
b. False.
5. Depending on the circumstances, partial agonists may behave like relative
antagonists.
a. True.
b. False.
6. Reuptake inhibition decreases the synaptic concentration of a
neurotransmitter.
a. True.
b. False.
7. Neuronal depolarization decreases the likelihood of a neuron generating an
action potential.
a. True.
b. False.
8. Receptor density on neurons is stable and static.
a. True.
b. False.
9. Addiction may be mediated in part by the tuberoinfundibular pathway.
a. True.
b. False.
10. Acetylcholinesterase synthesizes acetylcholine from choline and acetyl
coenzyme A.
a. True.
b. False.
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11. Nicotinic acetylcholine receptors are found in both the peripheral and central
nervous systems.
a. True.
b. False.
12. Dopamine pathways include the tuberoinfundibular, the mesocortical limbic,
and the nucleus basalis of Meynert-hippocampal pathways.
a. True.
b. False.
13. Kainate receptors are coupled to G proteins.
a. True.
b. False.
14. N-methyl-D-aspartate receptors bind to glutamate.
a. True.
b. False.
15. Melatonin is released from the suprachiasmatic nucleus.
a. True.
b. False.
Answers to True-False Questions
1. True
2. True
3. False
4. True
5. True
6. False
7. False
8. False
9. False
10. False
11. True
12. False
13. False
14. True
15. False
Short Answer/Essay Questions
1. Discuss the potential outcomes of a neurotransmitter being released into a
synapse.
2. Describe the putative roles of serotonin 1A, 2, and 3 receptors.
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3. Discuss the monoamine hypothesis of depression.
4. Discuss the three main dopamine pathways.
5. How do GABAA agonists lead to neuronal hyperpolarization?
6. Why can a neurotransmitter have more than one effect?
7. Compare and contrast the putative functions of serotonin and norepinephrine.
8. What are the functions of the brain’s endogenous opiate system?
9. How are synaptic concentrations of a neurotransmitter regulated?
10. Describe how a partial agonist could have both antagonist and agonist
properties.
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