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Chapter 4
Electrical to Chemical Signal to Electrical/Psychopharmacology
The players:
a) Ion channels:
1) Signals that __transduce__ (change from one signal type to another)
a) Ligand Gated
a. Ligand = a chemical that attaches to a binding site on a receptor
b. Found in dendrites, cell body and axon terminal
b) Mechanically Gated
a. Found in sensory systems (example: skin)
2) Signals that ___propogate___
c) Voltage Gated
a. Found all throughout neuron membrane
b. Propagate post-synaptic potentials and action potentials
b) Receptors:
NT receptor
Directly/indirectly
Speed of
location?
opens channel?
action?
On channel
Directly
Fast
Ionotropic (ligand
- via NT
receptor)
Coupled to GIndirectly
Slow
Metabotropic (g protein
protein
- via alpha subunit
coupled receptor)
Length of action?
Short
Long
c) Neurotransmitters; their lifecycle:
1. Biosynthesis
a. Differs for each neurotransmitter but each begins with precursor + enzyme = NT
2. Storage
a. Vesicles are created in the golgi apparatus
b. Precursors, enzymes, and vesicles are transported down the axon to the terminal (microtubules)
c. Once in the terminal, NT are synthesized and packaged into vesicles
3. Release (See below)
4. Receptors [See above (iono vs. metabotropic) ]
5. Inactivation
a. Destruction (enzymes break NT down)
b. Diffusion (the process by which molecules spread from areas of high concentration, to areas of low
concentration)
c. Reuptake (by presynaptic receptors). For a picture: pg. 61
c.2) For specific neurotransmitters, see chart below
d) Regulation of axon terminal activity (how does a neuron know its fired too much or too little)
1. Autoreceptor:
a. Definition: Metabotropic receptors on the presynaptic neuron that respond to the neurotransmitter that
they themselves release
b. Purpose: to regulate the synthesis and release of the neurotransmitter; mostly inhibitory effects that is the
presence of that NT causes a decrease in the rate of synthesis or release of the NT
c. Picture: pg. 113, more information in chapter 2 pg. 63
2. Heteroreceptor:
a. Definition: Activation of neuron 1’s terminal button causes presynaptic inhibition OR facilitation of the
neuron 2’s terminal button. The second neuron contains heteroreceptors that are sensitive to the NT
released by neuron 1.
b. Purpose: also to regulate synthesis and release of neurotransmitter possibly through regulating Ca++
c. Example: Endorphins, Picture: pg. 113
3. Retrograde signaling
a. Definition: Post-synaptic cell sends messengers back to the presynaptic cell
b. Example: If a post-synaptic neuron is receiving too much input, they may snip off a NT like 2-AG which
resides in the cell membrane of the post-synaptic neuron. The 2-AG NT will float back to the pre-synaptic
cell and bind to CB1. CB1 will slow down the entry of Ca++ to the cell.
The Game Plan
WHAT?
1. Action potential
2. Na+ influx
3. Ca++ influx
4.
5.
6.
7.
8.
9.
10.
11.
12.
Vesicles
NT
Receptors
Ion channels
Ions
Membrane potential
EPSP and IPSP
Membrane potential
Action potential
ACTION?
arrives at the ___terminal button_____
causes opening of voltage-dependent/gated __Ca++__ channels
severs __anchoring proteins__ and causes vesicles to fuse with presynaptic membrane
release NT via __exocytosis__
diffuses across synaptic cleft
bind NT
open
move
changes (__EPSP__ if depolarized, __IPSP__ if hyperpolarized)
summate
reaches threshold
propagates
Psychopharmacology (routes of administration of drugs and their fate in the body) [i.e. Big picture]
- Psychotropics: drugs affecting perception, mood and behavior
- Pharmacokinetics: the process by which drugs are absorbed, distributed, metabolized, and excreted within the
body
o Administration:
 Injection (in muscles, underneath the skin, veins and more)
 Oral (sublingual, inhalation)
 Topical (directly into the skin, steroids)
o Measurement:
 Blood plasma
 Microdialysis
o Distribution:
 Properties that affect absorption
 Lipid solubility: molecules that are lipid soluble pass through cells easily & quickly
 pH
 Impediments to drugs
 MAO in gut (will break down monoamines and inactivate certain NT)
 Depot binding
o Blood albumin: if the molecule is bound to a depot (like albumin) they cannot reach
their sites of action
o Fat cells: another example, most slowly, and less likely to interfere with the initial
effects of the drug
 Blood brain barrier: only lets fat soluble molecules pass; the faster a drug can get pass this the
better the “high”
- Psychodynamics: effect the drug exerts
Drug Effectiveness
-How to measure?
Dose Response Curve:
Therapeutic Index: ratio of a lethal dose to effective dose:
High therapeutic index ratio = drug relatively safe
(because you need a lot of the drug for it to be lethal)
Low therapeutic index ratio: BE CAREFUL.
Sites of Action: What are the many ways drugs can affect you?
Agonist
-chemical that facilitates post-synaptic
effects
-example: AChE
(acetylcholinesterase) breaks down
ACh. In a patient with ACh deficit,
can block enzyme so that ACh can
continually stimulate a post-synaptic
cell. So a chemical that blocks AChE
is a ACh agonist.
Antagonist
-chemical that block or inhibit postsynaptic effects
-example: a choline reuptake blocker
would prevent choline from reentering the cell thereby preventing the
re-synthesis of ACh
Drugs can be either:
Indirect
-chemical that binds to a receptor site other than the
primary receptor site or indirectly affects the effectiveness
of a drug
-example: benzodiazepines promote the activity of the
GABAa receptor and therefore is an indirect agonist
Non-competitive binding
-a receptor has a separate neuromodulator binding site. The
molecule does not compete with molecules of
-example: GABAa has a separate receptor for specific
drugs (benzodiazepine)
Inverse Agonist
-chemical that binds to the receptor
site of an agonist but reverses the
activity of the receptor
-example: if a zinc ion binds with the
zinc binding site on an NMDA
receptor, the activity of that receptor is
decreased
Direct
-chemical that binds directly to the primary binding site and
directly affects the effectiveness of a drug
-example: muscimol binds to the GABA binding site and
serves as a direct agonist.
Competitive binding
-drug binds at the exact same receptor site as a
neurotransmitter
-example: direct agonist
NT
E/I
Amino acids
Glutamate +
GABA -
Precursor
Glutamine
Byproduct of
Krebs
Glutamate
Receptor type
I: NMDA, AMPA, kainate
M: metabotropic glu receptor
[NMDA: 6 binding sites: (glu, gly,
polyamine, zinc, mg, PCP), also
known as an AND gate= will only
open if there is depolarization and glu
binds]
I: GABAa (controls Cl-)
M: GABAb (controls K+)
Inactivation
Reuptake
Reuptake
Function
Sensory motor
Direct excitatory effects in
brain and spinal cord raise
or lower the threshold of
excitation affecting the rate
of action potentials
Brain pathway
Everywhere
Cortex  cortex
Direct inhibitory effects
throughout brain and spinal
cord
Cortex  cortex
Modulatory
-Primary NT secreted by
efferent axons in CNS and
1st discovered
-Help learning (basal)
-Form memories (medial)
-REM sleep (pons)
-Arousal
-Attention
-Increases vigilance
Midbrain  Cortex
-Basal forebrain 
-Medial septum 
-Pons 
-Movement
-Nigrostriatal pathway:
Substantia nigra  striatum (BG)
-Mesocortical: VTA Cortex
-Mesolimbic: VTA  Limbic
[GABAa, at least 5 binding sites:
(GABA, benzodiazepine, steroid,
picrotoxin, barbiturate)
Biogenic amines
Acetylcholine +
(ACh)
Choline &
Acetyl CoA
Norepinephrine +
(NE) (ge
Catecholamine ner
al)
Dopamine (DA)
Catecholamine +
-
Tryosine 
L-DOPA
Dopamine
NE
Tyrosine
(AA) 
L-DOPA
Serotonin +
(5-HT)
Indolamine
Neuropeptides/
Opioids
(ex.
Endorphins)
-
I: nicotinic; in skeletal muscles
-agonized by: nicotine
-antagonized by: curare
M: muscarinic; in smooth muscle
-agonized by: muscarine
-antagonized by: atropine
M: α1 & β1-2 (post-syn, excitatory)
α1 (autoreceptor, inhibitory)
M:
D1 (post-synaptic)
D2 (pre & post-synaptic)
-AChE
(acetylcholin
esterase),
eventual
reuptake of
choline
Reuptake,
MAO
(monoamine
oxidase)
Reuptake,
MAO
-Working mem/planning
Tryptophan
9 types
All metabotropic but 1
Reuptake,
MAO
Amino acids
3 all Metabotropic:
mu: most analgesic effects
delta: some analgesic effects
kappa: negative side effects
Enzymes (no
reuptake)
-Reinforcement/addiction
-Mood, social cognition
-Suppresses certain
categories of speciestypical behavior
-Act as both NT and NM
-Modulation of effects of
other NT
Locus coeruleus (dorsal pons) 
EVERYWHERE!
Raphe nucleus (in pons, midbrain,
medulla)  cortex, basal ganglia,
hippocampus
-Used in combination with other
NTs
-Everywhere, esp. limbic