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chapter notes 5

Course Code
Suzanne Erb

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Chapter 5
-Specific neuroactive ligands are highly localized in some areas of the brain, while
others are distributed widely throughout the nervous system.
-By interacting with the natural neuroactive ligands in various areas of the brain,
drugs can shift normal psychological activities carried out by the brain into
abnormal ones and in some cases, can serve to normalize abnormal psychological
Neurotransmitters, Neuromodulators, and Neurohormones
-Neurotransmitters are commonly viewed as chemical that are located in specific
regions of neurons, are released under specific stimulation, act on a specific set of
receptors, and induce short-duration changes in membrane potential.
-Neurohormones, these are chemicals that are synthesized in one area of the
nervous system, are released into circulation, travel to some site that is distant
from the release site, and then produce some effect on the brain or body.
-There are chmicals that have some of the characteristics of neurotransmitters or
neurohormones, but by themselves have no intrinsic activity except in the
presence of other synaptic activity =Neuromodulators because they modify
response to other transmitter presynaptically or postsynaptically while not
showing any direct shifts in membrane potential or conductance when tested for
actions on their own. Eg. A neuromodulator may induce a change in the binding
of a neurotransmitter to its receptor, or it can act through secondary messengers to
modulate neural responses to a neurotransmitter.
-A chemical that appears to play the role of a neurotransmitter in one area of the
nervous system may play the role of a neuromodulator or neurohormone
somewhere else in the body.
-Hundreds of chemicals in the nerbous system have eeb indentified as either being
or having the potential to be neurotransmitter.
-They range in structural complexity from molecules of two atoms eg NO and CO
-The major chemical classes of transmitters are amines, amino acides, and
-With respect to the CNS, most of these chemicals have yet to meet several criteria
that would definitely indicate their roles as neurotransmitters.
In order for a chemical to be designated as a neurotransmitter:
1. It should be found in presynaptic neurons
2. Enzymes necessary for its synthesis must also be present in the neuron
3. There should a mechanism for terminating its action
4. Its direct application to the postsynaptic neuron should be equivalent to
stimulation of the presynaptic neuron

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5. When the presynaptic neuron is stimulated, the synaptic cleft should contain the
6. Drugs interfering with the synthesis or reaction at the postsynaptic membrane
should block the effects of the presnaptic neuronal stimulation and
7. Drugs blocking the action of the inactivating enzyme should prolong the
transmitter’s action
-Though most of the chemicals satisfy one or more of these criteria only Ach and
NE in the peripheral nervous system satisfy all of them
-Virtually every drug that alters psychological function does so by interacting with
one or more neurotransmitter systems in the brain.
-Drugs have been shown to alter the synthesis, storage, release, enzymatic
inactivation, and reuptake of the neurotransmitter.
-Many drugs either mimic (agonists) or block (antagonists) specific
neurotransmitters at their receptors, both presynaptic and postsynaptic.
-If the drug mimics the neurotransmitter at its postsynaptic receptor, it will
enhance the neurotransmitter’s ability to alter activity of the postsynaptic cell.
-If the drug mimics the action of the neurotransmitter at its auto-receptors and
inhibits the release of the neurotransmitter, it will reduce the neurotransmitter’s
ability to alter the activity of the postsynaptic cell.
-If a drug mimics a neurotransmitter at both its auto-receptor and its postsynaptic
receptors, but has a greater affinity for its auto-receptor—a situation that is nor
uncommon. The drug may reduce the neurotransmitter’s action at postsynaptic
receptor when administered in low doses (because activation of the auto-receptors
decrease the amount of endogenous neurotransmitter available for activating the
postsynaptic receptor), but it may activate the transmitter’s postsynaptic receptor
when administered in higher doses. In such cases, even though there is less
endogenous transmitter available for the receptor, the drug takes its place so that
there is more postsynaptic receptor activation that might occur normally with the
transmitter alone.
-One of the primary problems we currently have with respect to drugs is their
relative lack of speficity, which can result in dependence and side effects that
may, in the long run, be worse for patients than the condition they took the drug to
A psychoactive drug can alter any number of the processes involved in the
communication system. It can:
1. Increase or decrease the rate of synthesizing one of more neurotransmitters
2. Increase or decrease the amount of neurotransmitter released
3. Enhance or prevent the storage of neurotransmitter
4. Increase or decrease a neurotransmitter’s rate of metabolic breakdown.
5. Bind to the presynaptic or postsynaptic receptors for the neurotransmitter and,
depending on whether or not the drug activates the receptor, it can accentuate or blunt
the neurotransmitter’s effect
6. Reduce or enhance the neurotransmitter’s reuptake.

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7. Serve as a neurotoxin or neurotoxic agent, a substance that causes the destruction
of neural tissue.
Specific Neurotransmitters
-Serotonin is shown to be composed of an indole nucleus and an amine;
norepinephrine is shown to be composed of a catechol nucleus and an amine.
-Leu-enkephalin is shown to be composed of a string of amino acids; that is a
-Histamine is generally found in non-CNS cells made up of connective tissue
(mast cell)- and found in brain
-Although it shares a molecular similarity to the monoamines (norepinephrine,
domapine, serotonin), and blocking it action with antihistamines produces
substantial CNS actions such as drowsiness and hunger.
-Neurons are generally referred to by the neurotransmitter that is released that
plays the most predominant role in the process.
-Acetylcholine (Ach) was the first transmitter to meet all of the criteria listed at the
beginning of the preceding section.
-It is found in various parts of the PNS and numerous areas of the CNS
-It has excitatory properties in the PNS (depolarizes the membrane of target cells),
whereas in the CNS it can have either excitatory or inhibitory influences on
neuron, depending on the area being monitored.
-It is one of the transmitters that undergo inactivation in the cleft by
-Reuptake then occurs with one of the metabolites (choline)
-Cholinergic neurons are found in many different areas of the nervous system, and
it is likely that they play a role in a multitude of psychological activities.
-In the CNS, Ach is particularly important in memory functions
-Alzheimer’s disease, which results in severe memory loss, is due to the
destruction of a relatively small portion of Ach-containing neurons.
-Drugs that block Ach in the brain (anticholinergics) profoundly reduce the ability
to form new memories.
-Drugs that enhance Ach activity may be useful in alleviating some types of
memory dysfunctions.
-Ach is probably involved in certain forms of aggression and grand mal seizures,
since both have been notes to occur when there is excessive Ach activity.
-Cholinergic mechanisms play an important role in the initiation and maintenance
of REM sleep.
-Since abnormalities in REM sleep are found in clinical disorders such as major
depression, narcolepsy, obsessive-compulsive disorder, and some forms of
schizophrenia, it is possible that abnormal activation of central cholinergic
mechanism may be involved in these disorders.
- Ach also plays numerous roles in the PSN
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