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Spring 2012
Dr. Andre Ragnauth, Ph.D.
Course DirectorSDSBECCNY
HappyLosar
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the brain
Cortex
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Neurons
Santiago Ramn y Cajal (1852 1934)Spanish pathologist,histologist, neuroscientist,and Nobel laureate. His pioneering investigations ofthe microscopic structure of the brain were original;he is considered by many to be the father of
modern neuroscience. He was skilled at drawing,and hundreds of his illustrations of brain cells arestill used for educational purposes today.http://en.wikipedia.org/wiki/Santiago_Ram%C3%B3n_y_Cajal Cortex
Cerebellum
Purkinje cells Synaptic connectionsA Neuron
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Cartoon of interactions at a chemical synapse
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Structure of a typical chemical synapse
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Criteria for a Neurotransmitter
Localization A putative neurotransmitter must be localized to the presynaptic
elements of an identified synapse and must be present also within
the neuron from which the presynaptic terminal arises. Release
The substance must be shown to be released from the presynapticelement upon activation of that terminal and simultaneously withdepolarization of the parent neuron.
Identity Application of the putative neurotransmitter to the target cells must
be shown to produce the same effects as those produced bystimulation of the neurons in question.
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Steps in Synaptic Transmission That Are Affected by Drugs
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Steps in Synaptic Transmission That Are Affected by Drugs
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Cathecholamines
Dopamine (DA) Precursor of norepinephrine
Biological activity in the central nervous system and in theperiphery
Norepinephrine In the brain and in the sympathetic neurons
Epinephrine
Formed from norepinephrine Released by the adrenal gland
Stimulates receptors in several organs
D i i P h i h B i
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Dopaminergic Pathways in the Brain
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Dopaminergic Projection Systems
Mesolimbic tract
Nigrostriatal tract
Mesocortical
tract
http://www.beautifulfunnysadandtrue.com/how-do-you-say-dopamine-in-chinese/
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Dopamine (DA) Neurons
Nigro-striatal dopamineneurons
Cell bodies are in thesubstantia nigra
Project to striatum
Part of the extrapyramidalmotor system
Motor balance, gait andmuscle coordination and
control Die (degenerate) in
Parkinsons disease
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Dopamine Neurons
Mesocorticolimbicdopamine neurons Cells bodies as in the
ventral tegmental area(VTA)
Project to the nucleus
accumbens, the frontalcortex and theamygdala
Involved in reward and
reward seekingbehaviors Targets for many drugs
of abuse
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Dopamine Synthesis and Storage in nerve terminals
DA
Cell Body (VTA)
Projects to
Nerve terminal(nucleus accumbens)
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Dopaminestorageandrelease
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Dopaminereleaseand
recovery
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Dopamine and Cocaine
Cocainebinds to DAT Blocks DA
transport Increases
dopamineconcentration in thesynapticcleft
Results inincreased andprolongedactivation ofDA receptors
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Synapse: Dopamine
Dopamine
binding toreceptorsand uptakepumps inthe nucleusaccumbens
http://www.nida.nih.gov/pubs/teaching/largegifs/slide-12.gif
DA
DA receptor
DA reuptake pumps
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Cocainebinding touptakepumps:inhibition
ofdopamineuptake
http://www.nida.nih.gov/pubs/teaching/largegifs/slide-13.gif
DA
Synapse: Dopamine + Cocaine
DA receptor
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IncreasedcAMPproducedin post-synapticcell
http://www.nida.nih.gov/pubs/teaching/largegifs/slide-14.gif
cAMP
Synapse: Dopamine + Cocaine = postsynaptic effects
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Dopamine and Cocaine
Cocaine binds toDAT
Blocks DAtransport
Increases
dopamineconcentration inthe synapticcleft
Results in increasedand prolongedactivation of DAreceptors
http://schizophreniasymptoms.net/dopamine-receptors/
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Dopamine and Amphetamine
Competes with DA forthe DAT
Transported into the
DA containing vesiclesby VMAT
Inhibits MAO
Displaces DA from thevesicles
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MAO and antidepressants
Blocks thedegradationof DA
Used totreatclinicaldepression
and panicdisorders
MAO Mono-Amine Oxidase
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http://www.viewzone.com/dopamine.html
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Norepinephrine (NE)
neurons are a so part o t e
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neurons are a so part o t e
sympathetic nervous system
Fight or flightresponse
NE neurons are
contained in ganglia(small mass of nervetissue containing thecell bodies ofneurons) and these
neurons send longnerve fibers to thetarget tissues.
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Actions of NE
Supply many tissues to cause excitatoryresponses:
Increase excitability of cardiac muscle and heart rate
Constrict blood vessels causing an increase in blood
pressure Relax airways making it easier to breathe
Dilate pupils
Stimulates secretion epinephrine from the adrenal gland
Stimulate glucose production by liver Inhibits the gastrointestinal tract
Inhibits salivary secretion
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NE &d b
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NE &drug abuse Cocaine blocks NET
Contributes toincreased
attentiveness, loss ofappetite and lack ofsleep
Amphetaminetransported by theNET, taken up intothe vesicles Same effects
Someantidepressantsblock NET
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Cocaine & Amphetamine: Psychomotor Stimulants
Both increase sympathetic nervous system signaling totarget tissues
Increased heart rate
Increased blood pressure
Increased respiration
Increased pupil dilation Inhibition of gastrointestinal tract
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Indolamines
Serotonin (5HT) Derived from Tryptophan
Biological activity in the GI tract, blood platelets & thecentral nervous system.
Regulates mood, appetite & sleep
Melatonin
Found in animals, plants & microbial life
Regulates circadian rhythms
Potent antioxidant & protector of DNA
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Serotonin (5-HT) in the brain
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Synthesis of Serotonin (5-HT)
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Release and recovery of 5HT at the synapse
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5-HT and MDMA (ecstasy) MDMA
causes the release ofthe neurotransmitterserotonin.
blocks the reuptake of
serotonin by thesynaptic terminal thatreleases it.
depletes the amount
of serotonin in thebrain.
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5-HT and LSD (acid)
LSD mimics serotonin during the transmission process but does
not cause suppression
lead to hallucinations, visual after-images, distortions ofperception and eventually paranoia
LSD molecules are reabsorbed by the neuron for repeated"flashback" activity and persistent perceptual distortion Can get flashbacks up to a year after use
Cells of the associate visual cortex are particularly susceptible
LSD may be a last resort treatment for extreme depression
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5-HT - targets for a variety of therapeutic drugs
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Potential Changes Drugs can have on Neurotransmitters
Change inneurotransmission
Effect onneurotransmitter
release oravailability
Drug that acts this way
increase the number ofimpulses
increased neurotransmitterrelease
nicotinealcoholopiates
Release neurotransmitter
from vesicles with orwithout impulses
increased neurotransmitter
release
Amphetamines
methamphetamines
Release neurotransmitter inresponse to impulses
increased neurotransmitterrelease
Nicotine
Block reuptake more neurotransmitter
present in synaptic cleft
Cocaine
amphetamine
block receptor with anothermolecule
No change inneurotransmitter release orneurotransmitter cannotbind to its receptor on the
post synaptic neuron
LSDcaffeine
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Drugs and Reward
http://learn.genetics.utah.edu/content/addiction/drugs/mouse.html
http://learn.genetics.utah.edu/content/addiction/
http://www.youtube.com/watch?v=b17d_c9WANE&feature=related
http://www.youtube.com/watch?v=GiC-UuRwZFQ